CN112274525B - A kind of chemotherapeutic composition and its application - Google Patents

Abstract

The invention relates to the technical field of biological medicines, in particular to a chemotherapeutic medicine composition and application thereof. A chemotherapeutic composition comprises cepharanthine and epirubicin. Before administration of epirubicin, cepharanthine is administered to synergistically enhance the cancer cell inhibitory effect of epirubicin. The scheme solves the technical problems that the epirubicin has limited curative effect and the cancer patients are easy to generate adverse reaction and drug resistance after long-term use. The composition can be applied to clinical practice of treatment of various cancers, reduces adverse reactions of epirubicin and simultaneously prevents the appearance of drug resistance of epirubicin.

Description

A kind of chemotherapeutic drug composition and its application

technical field

The invention relates to the technical field of biomedicine, in particular to a chemotherapeutic drug composition and application thereof.

Background technique

Chemotherapy is one of the methods for the treatment of malignant tumors (cancer). Epirubicin (Epirubicin), also known as epirubicin, compared with doxorubicin (Doxorubicin), higher efficacy, but less toxicity to the heart, is one of the currently clinically used chemotherapy drugs. Epirubicin injection is clinically used for the treatment of breast cancer, ovarian cancer, digestive tract cancer (such as advanced gastric cancer, advanced rectal and colon cancer), malignant lymphoma, lung cancer and malignant melanoma. However, epirubicin, like other chemotherapeutics, due to its weak selectivity, will inevitably damage normal cells of the human body while killing cancer cells, resulting in adverse drug reactions. After all, the treatment time for malignant tumors is relatively long, and in the long-term treatment process, drug resistance or drug resistance will inevitably develop gradually. How to improve the curative effect of epirubicin without increasing the dosage of epirubicin, thereby reducing the adverse reactions of epirubicin, and preventing the emergence of drug resistance at the same time, this is the use of epirubicin etc. Difficulties to be overcome in the treatment of cancer with chemotherapeutic drugs.

SUMMARY OF THE INVENTION

The present invention is intended to provide a chemotherapeutic drug composition to solve the technical problems of limited curative effect of epirubicin and long-term use of epirubicin in cancer patients prone to produce adverse reactions and drug resistance.

To achieve the above object, the present invention adopts the following technical solutions:

A chemotherapeutic drug composition comprising fenugreek and epirubicin.

The principle and advantages of this program are: Epirubicin (Epirubicin, cas: 56390-09-1) is a commonly used anticancer chemotherapy drug in clinical practice. Enhancement of the cancer cell inhibitory effect of epirubicin. Cepharanthine (Cepharanthine, CEP, cas: 481-49-2) is an isoquinoline alkaloid extracted from the roots of the plant of the fangchiaceae plant, Cepharanthine. Under normal doses, fenugreek is a drug with basically no toxic side effects, and only occasional gastrointestinal reactions have been seen in clinical practice, and no significant toxic and side effects have been seen. The use of fenugreek can reduce the dosage of epirubicin on the basis of ensuring the efficacy of epirubicin, reduce the adverse reactions caused by excessive use of epirubicin, or prevent the human body from producing epirubicin resistance. Medicinal properties.

In conclusion, fenugreek can synergize with the clinical chemotherapeutic drug epirubicin to improve its effect of inhibiting and killing various tumor cells. Experiments have shown that breast cancer MDA-MB-231 cells, MCF-7 cells, BT549 cells, leukemia K562, U937 cells, gastric cancer SGC-7901 cells, lung cancer A549 cells, esophageal cancer Eca109 cells, in the case of using fenugreek , the effect of epirubicin in inhibiting and killing these tumor cells has been greatly improved, and the effect of fenugreek combined with epirubicin is significantly better than that of fenugreek combined with doxorubicin, epirubicin combined with chloroquine Effect.

Further, the mass ratio of fenugreek and epirubicin was 0.97:0.032.

By adopting the above technical scheme, the above mass ratio of fenugreek and epirubicin can effectively inhibit the formation of tumor cells. When the combination of fenugreek and epirubicin is used to treat tumors, the mass ratio of the total amount of fenugreek and the total amount of epirubicin is 0.97:0.032.

Further, the single dose of fenugreek in human body is 0.97 mg/kg·bw.

Further, the single human dose of epirubicin is 0.16 mg/kg·bw.

By adopting the above technical scheme, the human single dose of fenugreek and epirubicin is obtained through the results of animal experiments and conversion. In Experimental Example 2, the single dose of fenugreek in nude mice was 12 mg/kg·bw, and the single dose of epirubicin in nude mice was 2 mg/kg·bw. The conversion basis is given by the U.S. Food and Drug Administration (FDA) in Estimating the Safe Starting Dose in Clinical Trials for Therapeutics in Adult Healthy Volunteers. The conversion ratio (1:12.3) of the injection dose between human and mice (that is, nude mice in experimental validation) required to achieve the same biological effect.

Further, in a course of treatment, the ratio of the times of administration of fenugreek to epirubicin is 5:1.

By adopting the above-mentioned technical scheme, the use of low-toxic fenugreek can reduce the administration frequency of epirubicin and reduce the harm of chemotherapy drugs to the human body.

Further, the administration routes of fenugreek and epirubicin are both intravenous administration.

By adopting the above technical scheme, intravenous injection is the conventional mode of administration of fenugreek and epirubicin. When injecting the epirubicin injection in the combination medicine of the present invention, it is actually the same discontinuous administration method as the single epirubicin injection. Because the drug epirubicin is metabolized for a long time in the human body, discontinuous administration can reduce the toxic and side effects. Even if the drug combination is formed by synergy with fenugreek, the dosage of epirubicin can already be reduced, but this method of medication is still used, which is in line with traditional medication habits and is more convenient. When applying the drug combination of the present invention, only the step of injecting fenugreek injection is added, and there is no other special operation method. The actual dosage of fenugreek in the pharmaceutical combination of the present invention is much more than that of epirubicin. Combined with the experimental verification, it can not only show that the use of fenugreek in conjunction with epirubicin to inhibit and kill various malignant tumor cells can reduce the dosage of drugs, shorten the treatment period, and reduce the occurrence of toxic and side effects. Even conversely, under the mediation of the existing clinical chemotherapeutic drug epirubicin, the fenugreek found by the inventors of the present application, which can effectively block the autophagic degradation of various tumor cells, also has an effect. Reliable and practical value in killing various malignant tumor cells.

Further, the application of a chemotherapeutic drug composition as an anticancer drug, the chemotherapeutic drug composition comprising fenugreek and epirubicin.

By adopting the above technical solution, since fenugreek and epirubicin have the effect of synergistically enhancing the killing effect of cancer cells, they can be used in the preparation of anticancer drugs.

Further, the anticancer drug is used for the treatment of triple negative breast cancer.

Using the above technical solution, the combined use of fenugreek and epirubicin has a significant inhibitory effect on human triple-negative breast cancer cells MDA-MB-231 and BT549 cells, while sensitizing non-triple-negative breast cancer cells MCF-7 cells The effect is relatively weak, so fenugreek and epirubicin can be used in the treatment of triple negative breast cancer. The combination of fenugreek and epirubicin showed a good inhibitory effect on triple-negative breast cancer cells. Triple-negative breast cancer refers to breast cancer whose cancer tissue immunohistochemical examination results are negative for estrogen receptor (ER), progesterone receptor (PR) and proto-oncogene Her-2. The disease has a poor prognosis and death. Higher risk.

Further, in a course of treatment, the administration frequency of fenugreek was 20 times, and the administration frequency of epirubicin was 4 times.

By adopting the above technical scheme, the use of the low toxicity fenugreek can reduce the administration frequency of epirubicin.

Further, in a course of treatment, the dosing frequency of fenugreek is once a day, and the dosing frequency of epirubicin is once every 5 days.

By adopting the above-mentioned technical scheme, the use of low toxicity fenugreek can reduce the administration frequency of epirubicin.

Description of drawings

FIG. 1 is the cancer cell inhibition curve of epirubicin alone and epirubicin combined with fenugreek in Experimental Example 1 (the experimental object is breast cancer cells, and the concentration of fenugreek is a fixed value).

FIG. 2 is the cancer cell inhibition curve of fenugreek alone and fenugreek combined with epirubicin in Experimental Example 1 (the experimental object is breast cancer cells, and the concentration of epirubicin is a fixed value).

FIG. 3 is a statistical graph of the cancer cell inhibitory effect of epirubicin and doxorubicin in experimental example 1 in combination with fenugreek, respectively.

Figure 4 is a statistical graph of the inhibitory effect of fenugreek and chloroquine in Experimental Example 1 in combination with epirubicin, respectively.

5 is a statistical graph of the cancer cell inhibitory effect of epirubicin combined with fenugreek in Experimental Example 1 (for cells other than breast cancer cells).

FIG. 6 is a photograph of mice in different experimental groups of Experimental Example 2 (showing tumor volume).

FIG. 7 is a graph showing the change in tumor volume of experimental mice in Experimental Example 2. FIG.

FIG. 8 is a graph showing the change in body weight of experimental mice in Experimental Example 2. FIG.

Detailed ways

The following is further described in detail by specific embodiments:

Example 1:

A chemotherapeutic drug composition of the present scheme is composed of septilaginine and epirubicin, more specifically, the drug combination includes septilaginine and chemotherapeutic drug epirubicin. See formula (I) for the structural formula of fenugreek, and see formula (II) for the structural formula of epirubicin.

After knowing that the drug combination provided by the present invention can improve the curative effect and reduce adverse reactions, when the drug combination of the present invention is used to avoid drug resistance or drug resistance, those skilled in the art are fully capable of targeting specific malignant For tumors, the ratio between the two components, fenugreek and epirubicin, was determined only through limited routine experiments. For the several malignant tumor cells selected in the experimental verification of the present invention, it is appropriate to adopt such a ratio for the drug combination. In a course of treatment, the total dose of fenugreek: the total dose of epirubicin=0.97 : 0.032. The above-mentioned dose ratios are converted based on the animal experimental doses (Experimental Example 2). The conversion basis is given by the U.S. Food and Drug Administration (FDA) in Estimating the Safe StartingDose in Clinical Trials for Therapeutics in Adult Healthy Volunteers. The conversion ratio (1:12.3) of the injection dose between human and mice (that is, nude mice in experimental validation) required to achieve the same biological effect.

When using the drug combination of this scheme for treatment, fenugreek and epirubicin are administered in divided doses (but the ratio of the total doses is maintained at 0.97:0.032), and the specific application methods are as follows:

①According to the dose of fenugreek: patient body weight = 0.97mg/kg (it is necessary to use normal saline or 5% glucose injection to prepare fenugreek into fenugreek injection, this example uses physiological saline), through intravenous Inject fenugreek injection once a day;

②On the day of injection of fenugreek injection according to step ①, according to the dose of epirubicin: patient weight = 0.16 mg/kg (physiological saline or 5% glucose injection should be used to prepare epirubicin as epirubicin Star injection, the glucose injection used in the present embodiment), by intravenous injection of epirubicin injection once;

③ On the sixth day, according to the dose described in step ②, inject the same dose of epirubicin injection intravenously again; follow steps ① to ③;

④From the 21st day, according to the patient's body's ability to bear and the treatment effect, determine whether to follow the steps ① to ③ again, as well as the number of cycles and the intermediate withdrawal time.

Those skilled in the art are very clear that the concentration of the injection should be determined according to factors such as the patient's body's ability to withstand. It is 1 to 2 weeks; for patients with particularly poor health, steps ① and ② can even be used as a medication cycle or a course of treatment (that is, the medication is suspended from the sixth day).

Experimental Example 1: Cell Experiment

1. Cell Selection and Viability Culture

The experimental selections include human breast cancer cells MDA-MB-231, MCF-7, BT549, human leukemia cells K562, U937, human gastric adenocarcinoma cells SGC-7901, human lung cancer cells A549, and human esophageal cancer cells Eca109. Among them, human breast cancer cells MDA-MB-231, MCF-7, BT549 cells, human gastric adenocarcinoma SGC-7901 cells, and human lung cancer A549 cells were actively cultured in DMEM+10% FBS complete medium; human leukemia cells K562, U937 Cells, human esophageal cancer cells Eca109 were cultured in RPMI1640+10% FBS complete medium. The above cells were cultured in a cell culture incubator at 37°C, 5% CO ₂ , and saturated humidity.

2. Experimental methods and results

After each tumor cell line was stabilized, the cells were plated in 96-well plates with 5000 cells per well, and each well contained 90 μL of complete medium, and then the cells were treated with drugs. MTT assay was performed on the treated cells to determine the effect of drugs on cell viability: 48 hours after drug addition, 5 mg/mL of thiazolyl blue (MTT) prepared in 20 μL of phosphate buffer solution (PBS solution) was added to each well. The solution was incubated for an additional 4 hours. Aspirate the upper medium (human leukemia K562 and U937 cells were first centrifuged to the bottom of the well for human leukemia K562 and U937 cells), add 150 μL of dimethyl sulfoxide (DMSO) to each well to dissolve, and dissolve on the shaker for 10 minutes. The absorbance value was detected at A495 with a microplate reader, and the cell viability was calculated according to the following formula:

Percentage of cell survival=(absorbance of treatment group-absorbance of blank well)÷(absorbance of control group-absorbance of blank well)×100%.

The specific experimental grouping method is as follows:

Human breast cancer cells MDA-MB-231, MCF-7, BT549 cells were grouped and processed as follows:

(1) Control group: 10 μL of complete medium solution was treated.

(2) Epirubicin group: Epirubicin solutions with concentrations of 0, 1, 2, 4, 6, and 8 μM (μmol/L) were prepared in complete medium, and 10 μL was added to each well to make the effect final. Concentrations were 0, 0.1, 0.2, 0.4, 0.6, 0.8 μM. The experimental results are shown in Figure 1.

(3) The fenugreek group: the complete medium was used to prepare the fenugreek solution with the concentration of 0, 10, 20, 40, 60, 80 μM (μmol/L), and 10 μL was added to each well to make the final concentration of 0, 1, 2, 4, 6, 8 μM. The experimental results are shown in Figure 2.

(4) Combination drug group: epirubicin and fenugreek combination drug group

Two experimental protocols were used for the combination of epirubicin and fenugreek:

Scheme 1: Prepare epirubicin solution with concentration of 0, 1, 2, 4, 6, 8 μM and 20 μM fenugreek mixed liquid in complete medium, and add 10 μL of mixed liquid to each well to make the epirubicin soft. The final concentration of bicin was 0, 0.1, 0.2, 0.4, 0.6, 0.8 μM, and the final concentration of fenugreek was 2 μM. The experimental results are shown in Figure 1. Epirubicin itself has a certain concentration-dependent inhibitory effect on cancer cells, and under the action of fenugreek, the inhibitory effect of epirubicin at the same concentration is enhanced.

Option 2: Prepare 0, 10, 20, 40, 60, 80 μM solution of fenugreek and a mixture of 2 μM epirubicin in complete medium, and add 10 μL of the mixed liquid to each well to make fenugreek. The final concentration of epirubicin was 0, 1, 2, 4, 6, and 8 μM, and the final concentration of epirubicin was 0.2 μM. The experimental results are shown in FIG. 2 , fenugreek itself does not have a significant inhibitory effect on cancer cells, and with the increase in the amount of fenugreek, fenugreek does not show a cancer cell inhibitory effect. However, after adding 0.2 μM epirubicin, the composition has a significant effect of inhibiting cancer cells. This inhibitory effect is not only produced by epirubicin, but through the synergy of epirubicin and fenugreek effect realized. Combining Fig. 1 and Fig. 2, the single use of fenugreek has no obvious effect on the cell viability. Compared with the epirubicin group combined with epirubicin and the epirubicin group alone, the survival rate of tumor cells in the fenugreek combined with epirubicin group was lower than that in the epirubicin group alone. The effect of the combination is not additive, but the effect of 1+1 greater than 2.

Combining the experimental results of Figure 1 and Figure 2, the combination of fenugreek and epirubicin has a significant inhibitory effect on human triple-negative breast cancer cells MDA-MB-231 and BT549 cells, while on non-triple-negative breast cancer cells MCF The sensitization effect of -7 cells is weak, so fenugreek and epirubicin can be used in the treatment of triple-negative breast cancer. The combination of fenugreek and epirubicin showed a good inhibitory effect on triple-negative breast cancer cells.

(5) Combination drug group of doxorubicin and fenugreek

Doxorubicin solution with a concentration of 2 μM and a mixed liquid of 20 μM fenugreek were prepared in complete medium, and 10 μL of the mixed liquid was added to each well to make the final concentrations of 0.2 μM and 2 μM, respectively. The experimental results are shown in Figure 3. The final concentration of the fenugreek group is 2 μM; the final concentration of the epirubicin group is 0.2 μM; in the epirubicin + fenugreek group, the final concentration of epirubicin is 0.2 μM, the final concentration of fenugreek was 2 μM; the final concentration of doxorubicin group was 0.2 μM; in the doxorubicin + fenugreek group, the final concentration of doxorubicin was 0.2 μM, and the final concentration of fenugreek was 0.2 μM. The concentration is 2 μM. Doxorubicin and epirubicin are isomers, and the mechanism of action is to directly intercalate between DNA nucleobase pairs, interfere with the transcription process, prevent the formation of mRNA, and thereby inhibit the synthesis of DNA and RNA. The inventor's research found that when doxorubicin and epirubicin were used alone, the inhibitory effects on cancer cells were equivalent, but the combined effect of doxorubicin and epirubicin was significantly better than that of doxorubicin combined with fenugreek. Effect.

(6) Combination drug group of epirubicin and chloroquine

The epirubicin solution with a concentration of 2 μM and the mixed liquid of 40 and 200 μM chloroquine were prepared in complete medium, and 10 μL of the mixed liquid was added to each well. The concentration is 0.2 μM, the final concentration of chloroquine is 4 and 20 μM, and the final concentration of fenugreek is 2 μM. The experimental results are shown in Figure 4. The combined use of 4 μM chloroquine and 0.2 μM epirubicin cannot significantly inhibit the growth of cancer cells; while the combined use of 2 μM fenugreek and 0.2 μM epirubicin can significantly inhibit the growth of cancer cells. Inhibit the growth of cancer cells; increasing the dosage of chloroquine to 20 μM, the synergistic effect of chloroquine and epirubicin in inhibiting cancer cells is still not as good as the combination of fenugreek and epirubicin. Chloroquine (CQ) is an autophagy inhibitor, and chloroquine is the only autophagy inhibitor approved by the FDA for clinical use. Although both have the effect of inhibiting autophagy, when the two are used in combination with epirubicin, they have a very significant gap in promoting the tumor suppressor effect of epirubicin.

Human gastric adenocarcinoma SGC-7901 cells, human lung cancer A549 cells, human leukemia cells K562, U937 cells, and human esophageal cancer cells Eca109 were grouped and processed as follows:

(1) Control group: 10 μL of complete medium solution was treated;

(2) Epirubicin group: use complete medium to prepare epirubicin solution with a concentration of 2 μM (μmol/L), and add 10 μL to each well to make the final concentration of 0.2 μM;

(3) The fenugreek group: prepare the fenugreek solution with a concentration of 20 μM (μmol/L) in complete medium, and add 10 μL to each well for treatment; the final concentration is 2 μM;

(4) Combination drug group of epirubicin and fenugreek: the complete medium was used to prepare a solution of epirubicin with a concentration of 2 μM and a mixed liquid of fenugreek at a concentration of 20 μM, and 10 μL of the mixed liquid was added to each well. Its final concentrations were 0.2 μM and 2 μM, respectively.

The experimental results are shown in Figure 5. The combination of epirubicin and fenugreek can significantly inhibit the activity of human gastric adenocarcinoma SGC-7901 cells, human lung cancer A549 cells, human leukemia cells K562, U937 cells and human esophageal cancer cells Eca109.

In addition, in Figs. 3 to 5, the ordinate represents the cell viability, that is, the cell viability of the treated group relative to the control group. The abscissa is various human tumor cell lines (Note: only indicated by the distinguishing symbols of the corresponding tumor cells). The value corresponding to the bar is the average value of each group, and the "I" symbol in the figure indicates the upper and lower deviation.

In view of the experimental results in Figures 1-5, in order to prove that the verification conclusion is accurate and reliable, statistical calculation and analysis of the samples were also performed during verification. In the figure, "**" means p<0.01, where "p" is the boundary symbol of statistically acceptable error, and its value is p≤0.05. In the case of calculating p<0.01, it can be concluded that the survival rate of tumor cells in the group using fenugreek in combination with epirubicin is lower than that in the group using epirubicin alone, and the possibility of error is small. Naturally, this verification result is accurate and reliable.

Those skilled in the art are very clear that in cell experiments, the effect of drugs only has a corresponding relationship with the drug concentration, rather than the total amount of the drug. At the same time, the drug concentration at the cell level cannot be converted with the concentration in animal experiments. Therefore, , cell-level experiments can only verify whether there is a significant difference between the drug combination of fenugreek and epirubicin compared with epirubicin alone. Of course, this verification also fully proves the effectiveness and reliability of the drug combination of the present invention. When further verifying the effect of the drug combination of the present invention through nude mouse experiments, only one tumor cell was studied.

Experimental Example 2: Nude mouse xenograft model experiment (only taking human breast cancer MDA-MB-231 cells as an example)

During this experiment, various drugs were injected intraperitoneally into nude mice for comparison (ie not by intravenous injection).

1. Selection of nude mice

Twenty-four 6-8-week-old nude mice with no specific pathogenic microorganisms (SPF), with a weight range of 20 ± 2 g, were reared in an environment of alternating day and night at room temperature (20 ℃ ~ 23 ℃) with free access to water and food.

2. Experimental grouping and dosage (4 groups in total)

All nude mice were randomly divided into four groups, 6 mice in each group, and 1×10 ⁷ mice were inoculated with 0.2 mL of suspension prepared with human breast cancer MDA-MB-231 cells (human breast cancer MDA-MB-231 cells) on the outside of each right thigh. The culture is the same as the aforementioned "cell experiment"), and the drug is administered in the following manner after the tumor is formed.

(1) Control group: intraperitoneal injection of normal saline with the same volume as the treatment group, once a day;

(2) The fenugreek group: the nude mice were injected intraperitoneally with fenugreek at a dose of 12 mg/kg body weight, once a day;

(3) Epirubicin group: According to the dose of nude mice body weight 2 mg/kg, epirubicin was injected intraperitoneally, once every 5 days (that is, once every 4 days);

(4) The drug combination group of fenugreek and epirubicin: according to the dose of nude mice body weight of 12 mg/kg, intraperitoneal injection of fenugreek, once a day; on the same day as the first injection of fenugreek At a dose of 2 mg/kg of body weight of mice, epirubicin was injected intraperitoneally, once every 4 days.

The 0.16 mg in the above-mentioned epirubicin dose is the middle value of the ratio (0.03～0.04) of epirubicin in the aforementioned pharmaceutical combination of the present invention, and is calculated by injecting epirubicin once/5 days of.

The doses of fenugreek and epirubicin in the above groups only refer to the doses of the drugs themselves. The concentration that should be achieved when it is formulated into injection injection should be very clear to those skilled in the art, and at most can be determined through limited routine experiments, so it will not be described in detail.

3. Measurement and recording

(1) Measure and record the body weight of each group of nude mice every six days;

(2) After every six days, measure the length and width of the tumor with a vernier caliper, and record the volume of the tumor body of each group of nude mice; the tumor volume is calculated according to the following formula:

Tumor volume (mm ^{3 )} = tumor length (mm) × tumor width squared (mm ² )

The experimental results are shown in Figures 6-8. Figure 6 is taken after the end of the experiment (36 days). In Figure 7, the ordinate represents the tumor volume of each group of nude mice; the abscissa represents the measurement time point; Treatment group; the value of each point is the average value of tumor volume in each group (the "I" symbol in the figure indicates the upper and lower deviation). In Figure 8, the ordinate represents the average body weight of nude mice in each group; the abscissa represents the measurement time point; various line nodes represent each treatment group; the value of each point is the average body weight of each group.

As can be seen from Figure 7, compared with the epirubicin alone and the separatine alone group, the fenugreek in combination with epirubicin group, the tumor volume of the fenugreek in combination with epirubicin group was 12 to 18 days after treatment. Significantly lower than each drug alone group. The "**" in Figure 7 also means p<0.01, and it can also be determined that the tumor volume of the fenugreek combined with epirubicin group is less likely to cause errors than the single drug group and the control group. This verification result is also accurate. And reliable.

As can be seen from Figure 8, compared with epirubicin alone, fenugreek combined with epirubicin group and control group, the weight of mice in fenugreek combined with epirubicin group was significantly higher than that of other groups. There was no significant difference between the drug alone group and the control group. n.s represents p>0.05, that is to say, the probability of error is greater than 0.05 because the weight of the fenugreek combined with epirubicin group is different from that of the single drug group or the control group, because p=0.05 is the maximum acceptable error probability in statistics , so the error probability here is greater than 0.05, it cannot be determined that the body weight of the fenugreek combined with epirubicin group is different from that of the single drug group or the control group, that is, there is no significant difference.

The verification results recorded in Figure 7 prove that the combination of fenugreek and epirubicin chemotherapy is indeed superior to the use of epirubicin alone in inhibiting and killing human breast cancer MDA-MB-231 cells, which can naturally reduce the dosage , Shorten the treatment period and reduce the occurrence of toxic and side effects. Since no obvious toxic and side effects were found in the record in Figure 3, the verification results prove that the drug combination of fenugreek and epirubicin chemotherapy will at least not have as obvious toxic and side effects as epirubicin alone.

It is clear to those skilled in the art that after passing the verification of the aforementioned cell experiments, and now through the nude mouse xenograft model experiment on human breast cancer MDA-MB-231 cells, it can be fully demonstrated that fenugreek synergizes with epirubicin The chemotherapeutic drug combination has the same effect on human breast cancer BT549 cells, human leukemia K562, U937 cells, gastric cancer SGC-7901 cells, lung cancer A549 cells, and esophageal cancer Eca109 cells (there are differences, but also extremely small).

The above are only examples of the present invention, and common knowledge such as well-known specific technical solutions and/or characteristics in the solutions are not described too much here. It should be pointed out that for those skilled in the art, some modifications and improvements can be made without departing from the technical solution of the present invention, which should also be regarded as the protection scope of the present invention, and these will not affect the implementation of the present invention. effect and the applicability of the patent. The scope of protection claimed in this application should be based on the content of the claims, and the descriptions of the specific implementation manners in the description can be used to interpret the content of the claims.

Claims (3)

1. A chemotherapeutic drug combination is characterized by consisting of cepharanthine and epirubicin with the mass ratio of 0.97: 0.032.

2. The use of a chemotherapeutic combination according to claim 1 for the preparation of an anticancer drug, wherein said chemotherapeutic combination consists of cepharanthine and epirubicin.

3. The use of a chemotherapeutic combination according to claim 2 for the preparation of an anticancer drug for the treatment of triple negative breast cancer.

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