CN112137999A - Application of dronedarone hydrochloride in preparation of medicine for resisting digestive tract tumor - Google Patents

Abstract

The application discloses an application of dronedarone hydrochloride in preparing a medicine for resisting digestive tract tumors, wherein the dronedarone hydrochloride has a chemical name: the method comprises the following steps of firstly, specifically evaluating the effect of dronedarone hydrochloride in an esophageal cancer in-vitro experiment through the effect of dronedarone hydrochloride on an esophageal cancer cell line; and secondly, specifically evaluating the in-vitro inhibition effect of the dronedarone hydrochloride on the gastric cancer cell line through the effect of the dronedarone hydrochloride on the gastric cancer cell line, and comprehensively evaluating the effect of the dronedarone hydrochloride on the digestive tract tumor. The result shows that the dronedarone hydrochloride with proper concentration has better inhibition effect in a digestive tract tumor cell line, and provides a new idea and a new basis for treating and preventing tumors.

Description

Application of dronedarone hydrochloride in the preparation of anti-gastrointestinal tumor drugs

technical field

The application belongs to the field of biomedicine, and specifically relates to the application of dronedarone hydrochloride in the preparation of anti-gastrointestinal tumor drugs.

Background technique

Esophageal cancer (EC) is one of the eight most common malignant tumors in the world. According to the data from the World Health Organization and the International Agency for Research on Cancer (WHO/IARC), there were about 456,000 new cases of esophageal cancer in the world in 2012, accounting for all 3.2% of cancer incidence; about 400,000 deaths, accounting for 4.9% of all cancer deaths. China is a country with a high incidence of esophageal cancer and the highest mortality rate of esophageal cancer. Its incidence rate ranks fifth among all types of tumors in mainland China, and its mortality rate ranks fourth. The incidence of esophageal cancer in China has obvious regional differences. The absolute high incidence in some areas is in sharp contrast with the relatively low incidence in surrounding areas, which constitute the most typical epidemiological characteristics of esophageal cancer in my country. According to the 2018 epidemiological survey in China, the 5-year survival rate after esophageal cancer surgery is 5-20%. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological types of esophageal cancer. ESCC is the most common subtype in developing countries, and one of the main reasons for the low 5-year survival rate of esophageal squamous cells is due to the high recurrence rate after primary surgery. At present, the prevention of postoperative recurrence of esophageal cancer is mainly radiotherapy and chemotherapy. However, the serious side effects brought by radiotherapy and chemotherapy to the body make radiotherapy and chemotherapy prolong the life of patients and aggravate the prognosis of patients. bad condition. And the 5-year survival rate of esophageal cancer patients has not been significantly improved. Gastric cancer is one of the common digestive tract malignancies and the fourth most common cancer in the world. More than 70% of the disease occurs in developing countries, and the 5-year survival rate of patients is less than 20%, resulting in 1 million deaths every year worldwide. Although surgical resection and effective adjuvant therapy in the early stage of the disease have good therapeutic effects, gastric cancer is still a threat to patients due to the poor prognosis and low early diagnosis rate, and the serious side effects of radiation therapy and chemotherapy on the body. A major cancer of life and health. Therefore, the discovery of new gastric cancer drugs is of great significance.

N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]phenyl]-5-benzofuranyl]-methanesulfonamide (Dronedarone hydrochloride, Molecular formula: C31H45ClN2O5S, molecular weight: 593.217, CAS: 141625-93-6) is a new type of antiarrhythmic drug approved by the US FDA. It is reported in the literature as a multichannel blocker with various electrophysiological properties for the maintenance of sinus rhythm in patients with non-permanent atrial fibrillation.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide the application of dronedarone hydrochloride in the preparation of anti-digestive tract tumor medicines. Through in vitro experiments, a preliminary study on the relationship between dronedarone hydrochloride and tumors has been carried out, and it has been proved that dronedarone hydrochloride It has inhibitory effect on tumor cells. The tumors include but are not limited to esophageal cancer, gastric cancer and the like.

Based on the above purpose, the technical scheme adopted by the present invention is as follows:

1. Application of dronedarone hydrochloride in the preparation of drugs for inhibiting tumor cell proliferation

Specifically, when dronedarone hydrochloride is used in esophageal cancer cell lines KYSE150 and KYSE450, dronedarone hydrochloride can inhibit the proliferation of esophageal squamous cell carcinoma cells and the number and size of clone formation at a concentration of 1 μM to 2.5 μM. When dronedarone hydrochloride is used in gastric cancer cell lines HGC27 and AGS, dronedarone hydrochloride can inhibit the proliferation of gastric cancer cells and the number and size of colony formation at a concentration of 1 μM to 2.5 μM.

2. The application of dronedarone hydrochloride in the preparation of a drug for inhibiting tumor growth in mice in a human-derived esophageal squamous cell carcinoma xenograft model

Specifically, when dronedarone hydrochloride is used in esophageal cancer human-derived tumor xenograft models, when the dose is below 120 mg/kg/day, the toxic and side effects to animals are small. Can significantly inhibit tumor growth.

The general idea of the application is as follows: by treating gastrointestinal tumor cell lines with dronedarone hydrochloride, and observing the cytotoxicity and proliferation effect, the inhibitory effect of dronedarone hydrochloride on tumor cells is evaluated; The tumor xenograft model was treated with dronedarone hydrochloride, and the animal toxicity and tumor inhibitory effect were observed, so as to evaluate the inhibitory effect of dronedarone hydrochloride on the esophageal cancer human tumor xenograft model.

During the experiment, through in vitro experiments, the optimal concentration of dronedarone hydrochloride for each cell line was screened, and it was confirmed that dronedarone hydrochloride can strongly inhibit the cells of digestive tract tumor cell lines in the process of carcinogenesis. Proliferation and anchorage-independent growth. Through in vivo experiments, the optimal concentration of dronedarone hydrochloride for animals was obtained by screening, and it was confirmed that dronedarone hydrochloride can strongly inhibit the growth of esophageal cancer human tumor xenograft model.

The results show that the appropriate concentration of dronedarone hydrochloride has a good inhibitory effect on the proliferation of tumor cells and the growth of esophageal cancer human tumor xenograft model, which is the pharmacological effect of dronedarone hydrochloride and the treatment and prevention of tumors. Provided new ideas and new basis.

Description of drawings

Figure 1 shows the toxic effects of dronedarone hydrochloride on esophageal squamous cell carcinoma cells. When the concentration of dronedarone hydrochloride is in the range of 3.125 μM to 50 μM, the toxic effects of dronedarone hydrochloride on esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 are inhibited. effect; the figure shows the cell activity at different time points when the control group was 100% drugged with different concentrations.

Figure 2 shows the inhibitory effect of dronedarone hydrochloride on the proliferation of esophageal squamous cell carcinoma cells. When the concentration of dronedarone hydrochloride is in the range of 0 μM to 2.5 μM, dronedarone hydrochloride inhibits the esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450. Proliferation; the figure shows the proliferation curves of different concentrations of the drug at different time points. *p<0.05, **p<0.01, ***p<0.001.

Figure 3 shows the toxic effect of dronedarone hydrochloride on gastric cancer cells, wherein, when the concentration of dronedarone hydrochloride is in the range of 3.125 μM to 50 μM, dronedarone hydrochloride has a toxic inhibitory effect on esophageal squamous cell carcinoma cell lines HGC27 and AGS; The figure shows the cell viability at different time points when the control group was 100% dosed with different concentrations.

Figure 4 shows the inhibitory effect of dronedarone hydrochloride on the proliferation of gastric cancer cells, wherein, when the concentration of dronedarone hydrochloride is in the range of 0 μM-2.5 μM, dronedarone hydrochloride inhibits the proliferation of gastric cell lines HGC27 and AGS; Figure 4 In the middle is the proliferation curve of different concentrations of drug at different time points. *p<0.05, **p<0.01, ***p<0.001.

Figure 5 shows the effect of dronedarone hydrochloride on inhibiting the formation of esophageal squamous cell carcinoma cells. When the concentration of dronedarone hydrochloride is in the range of 0 μM to 2.5 μM, the effect of dronedarone hydrochloride on esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 With the increase of dosing concentration, the number of clones decreased significantly, and the clones became significantly smaller; the figure shows the microscope photos and statistical results of clones with different concentrations. *p<0.05, **p<0.01, ***p<0.001.

Figure 6 shows the growth inhibitory effect of dronedarone hydrochloride on esophageal cancer human-derived tumor xenograft models, the figure shows the effect of different concentrations of dronedarone hydrochloride on the body weight of mice and on tumor size, tumor volume, tumor weight inhibitory effect. *p<0.05, **p<0.01, ***p<0.001.

Detailed ways

The technical solutions of the present invention will be further described in detail below with reference to the examples, but the following examples are only used to illustrate the present invention and should not be used to limit the scope of the present invention.

1. Materials

1.1 Main reagents:

Dronedarone hydrochloride was purchased from Nantong Feiyu Biotechnology Co., Ltd. with a purity of 97%; cell culture medium was purchased from Thermo Fisher Scientific, USA; fetal bovine serum was purchased from BD Company, USA

1.2 Main instruments and equipment:

Dry _CO2 incubator, Shanghai Yiheng Scientific Instrument Co., Ltd.;

High-speed cryogenic centrifuge, Eppendorf, Germany;

High-content analysis imaging system In Cell Analyzer 6000, GE, USA

Inverted microscope, Carl Zeiss Jena, Germany

96-well cell culture plate, Wuxi Nice Biotechnology Co., Ltd.

2. Method:

2.1 Cytotoxicity experiment

Observe the cell state with a microscope, and the cytotoxicity test can be carried out when the state is good and the degree of confluence reaches 80%. Esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 cells and gastric cancer cell lines HGC27 and AGS cells were first washed twice with 5 ml 1×PBS, and then 1 ml 0.25% trypsin digestion solution was added to each 10 cm culture plate, 37 The cells were digested for 3-5 min in a cell incubator at ℃, tapped gently, and the cells were completely detached under a microscope. Add 5 ml of complete medium to terminate the digestion, collect the cell suspension into a 15 ml centrifuge tube, centrifuge at 1000 rpm for 3 min to discard the supernatant, add an appropriate amount of complete medium, suspend evenly and count with a hemocytometer to prepare a cell suspension to make the cell concentration of the cell suspension reach 12,000 cells/100 µl (KYSE450), 8,000 cells/100 µl (KYSE150), 6,000 cells/100 µl (HGC27), and 8,000 cells/100 µl (AGS) by gently pipetting until Cells are evenly distributed. Plate a 96-well plate and add 100 ml of cell suspension to each well to ensure that the number of cells plated in each well of the 96-well plate is 8000 cells/100 µl (KYSE150), 12000 cells/100 µl (KYSE450), 6000 cells/well 100 µl (HGC27), 8000 cells/100 µl (AGS) (KYSE150 cells: 10%FBS/RPMI-1640; KYSE450 cells: 10%FBS/DMEM; HGC27 cells: 10%FBS/RPMI-1640; AGS cells: 10 %FBS/F12K, 37°C, 5% CO ₂ ), the surrounding wells of the 96-well plate were sealed with 100 µl of 1×PBS, and the plate was placed in a cell incubator at 37°C, 5% CO ₂ after plating. . 16-18 h after the cells adhered (0 h at this time), the complete medium containing the drug was replaced according to the drug concentration setting (the drug was first dissolved in DMSO, and then dissolved in the medium at a ratio of 1:1000. The final concentrations in the base were 0 μM, 3.125 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM). The drug-containing medium was replaced at 0 h and 24 h, respectively, and the cell culture plate at the corresponding time was taken out at 24 h and 48 h. Remove the cell culture plate, discard the original medium, wash twice with 100 µl of 1×PBS, fix it with 100 µl of 4% paraformaldehyde for 30 min at room temperature, then discard, and then add 100 µl of 1×PBS Wash twice and keep 100 µl PBS at 4°C. After all cell culture plates were fixed, each well was stained with 100 µl of DAPI (1:3000 dilution) at 37°C for 20 min in the dark. After staining, washed twice with PBS and kept 100 µl of PBS in each well. Store at 4°C in the dark. Finally, the Analyze system 6000 was used to count, and the changes in the number of cells at 24 h and 48 h with different drug concentrations were counted, and a statistical chart was drawn. The results are shown in Figure 1 and Figure 3.

2.2 Cell proliferation experiment

2.2.1 Preparation of cell suspension

After the esophageal squamous cell carcinoma cell line was taken out of the incubator, the cell state was observed with a microscope, and the cytotoxicity experiment could be carried out when the state was good and the confluence reached 80%. Observe the cell state with a microscope. When the state is good and the confluence reaches 80%, the cell proliferation experiment can be carried out. Add 1 ml of 0.25% trypsin to each 10 cm culture plate, digest in a 37 ℃ cell incubator for 3-5 min, tap gently, and observe the cells under a microscope to completely fall off. Add 5 ml of complete medium to terminate the digestion, collect the cell suspension into a 15 ml centrifuge tube, centrifuge at 1000 rpm for 3 min, discard the supernatant, add an appropriate amount of 1640 complete medium, suspend evenly, count with a hemocytometer, and mix with cells Suspension, the cell concentration of the cell suspension reaches 5000 cells/100μl (KYSE450), 3000 cells/100μl (KYSE150), and gently pipetting until the cells are evenly distributed.

2.2.2 Seeding of cells

Plate a 96-well plate and add 100 µl of cell suspension to each well to ensure that the number of cells per well in the 96-well plate is approximately 3000 cells/100 µl (KYSE150), 5000 cells/100 µl (KYSE450), 3000 cells/100 µl (HGC27 ), 3000 cells/100 μl (AGS), (KYSE150 cells: 10%FBS/RPMI-1640; KYSE450 cells: 10%FBS/DMEM; HGC27 cells: 10%FBS/RPMI-1640; AGS cells: 10%FBS/F12K , 37°C, 5% CO ₂ ) Set 5 duplicate wells for each drug concentration, and seal the surrounding wells of the 96-well plate with 100 µl of 1×PBS. After plating, place the culture plate at 37°C, 5% CO ₂ in the cell incubator. The cells were plated for 16-18 h to adhere to the wall, and the cells adhered were recorded as 0 h. Every 24 h was set as an experimental cycle, so the medicated medium was changed every 24 h according to the drug concentration (the final concentration of the drug in the medium). 0 μM, 1 μM, 1.5 μM, 2 μM, 2.5 μM respectively) and fix the culture plate for the corresponding time until 96 h, and finally get the culture plate with dosing for 0, 24, 48, 72 and 96 h, and the experiment is over.

2.2.3 Fixation and staining of cells

Take out the cell culture plate, discard the original medium, wash twice with 100 µl of 1×PBS, fix it with 100 µl of 4% paraformaldehyde for 30 min at room temperature, then discard it, and add 100 µl of 1×PBS. Wash twice and keep 100 µl PBS at 4°C. After all cell culture plates were fixed, each well was stained with 100 µl DAPI (1:3000) at 37 °C for 20 min in the dark. After staining, washed twice with 1×PBS and kept 100 µl PBS in each well. Store at 4°C in the dark.

2.2.4 Results Statistics

Put the dyed 96-well cell culture plate into a high content analyzer for counting, and count the changes in the number of cells every 24 h, and draw a statistical graph. The results are shown in Figures 2 and 4.

2.3 Soft agar colony formation experiment

Experimental items: 10 µl, 200 µl, and 1 ml pipette tips, several 15 ml centrifuge tubes, 250 ml glass bottles, and several 1.5 ml EP tubes (all the above items need to be autoclaved). Fetal bovine serum, culture medium, BME, boiled agar gel, water bath at constant temperature of 45 °C.

2.3.1 Reagent preparation

After the 2×BME is prepared, put it in a 45°C water bath to preheat. The formula is as follows:

After the solute is completely dissolved, adjust the pH to 7.4, dilute to 500ml, and store at 4°C. 2×BME must be sterilized with a 0.22µM filter in a sterile environment before use.

The preparation of the lower layer glue:

After the addition of other reagents except agarose gel, the gel can be added only after a water bath for 20 min.

Formulation of 10% FBS-BME:

2.3.2 Experimental Procedure

After mixing the drug-containing lower layer glue (the drug concentration in the lower layer glue is 0, 1 μM, 1.5 μM, 2 μM, 2.5 μM in turn) and evenly suspending it, turn off the ultra-clean bench fan, and spread 3 ml per well into a 6-well plate. Two replicate wells were set up for each concentration. After spreading, stand at room temperature for 1 h. Remove the cells from the incubator, wash twice with 5 ml of 1×PBS, add 1 ml of 0.25% trypsin, digest in a 37°C cell incubator for 3-5 min, tap gently, and observe the cells completely fall off under a microscope. Add 5 ml of complete medium to stop digestion, collect the cell suspension into a 15 ml centrifuge tube, centrifuge at 1000 rpm for 3 min, discard the supernatant, and resuspend with 10% PBS-BME. After counting with a hemocytometer, a cell suspension with a concentration of 2.4×10 ⁴ cells/ml was prepared. Lay the upper layer of gel, take 2.4 ml of the lower layer of gel and 1.2 ml of cell suspension into a 15 ml centrifuge tube, add different concentrations of drugs (the drug concentrations in the upper layer of gel are 0, 1 μM, 1.5 μM, 2 μM, 2.5 μM) and mix well. Put it in 60 ℃ water, and after mixing, spread 1 ml per well into a 6-well plate to ensure that about 8000 cells per well are added to the gel. incubator. The growth of clones was observed every day, and photographed under a microscope for about 2 weeks, and the results were counted.

2.4 Establishment of human tumor xenograft model

Fresh esophageal cancer tumor tissue (patient from Henan Cancer Hospital, male, 46 years old, medical record number 2042083, stage T2N0M0Ⅱ, moderately differentiated squamous cell carcinoma) was discarded and necrotic tissue was discarded, cut into a diameter of about 3 cubic millimeters, and inserted into 6- 7-week-old Cb-17SCID immunodeficient female mice of about 18 g were subcutaneously on the back. Mice were housed in the mouse SPF barrier system. After waiting for the tumor to form about 15mm, the subcutaneous tumor was aseptically removed, and the solid mass was selected. Mice were killed by cervical dislocation, the skin around the mice was disinfected with 75% alcohol, a small incision was pricked with a drug-dissolving needle, and the removed tumor tissue was placed under the mouse's skin after being opened with tweezers.

When the growth status of the mice was normal, the tumor-bearing mice were randomly divided into 3 groups, the first group was the control group (40% polyethylene glycol + 60% normal saline), and the second group was the dronedarone hydrochloride low-dose group ( 30 mg/kg dronedarone hydrochloride was dissolved in 40% polyethylene glycol + 60% normal saline), and the third group was the high-dose dronedarone hydrochloride group (120 mg/kg dronedarone hydrochloride was dissolved in 40 % polyethylene glycol + 60% normal saline), according to this grouping, start to gavage every day, weigh once every 5 days and measure the tumor volume, tumor volume = (long diameter × short diameter × short diameter)/2. When the tumor tissue of the mice in the control group reached 1000 mm ³ , the experiment was terminated, the tumor tissue was taken out, the tumor weight was weighed and photographed for recording.

3. Results

1) Toxicity of dronedarone hydrochloride on esophageal squamous cell carcinoma cells (see Figure 1), among which, when dronedarone hydrochloride is in the concentration range of 3.125 μM-50 μM, dronedarone hydrochloride has an effect on esophageal squamous cell carcinoma cell lines KYSE150 and KYSE150. KYSE450 produced a toxic inhibitory effect, and with increasing concentration, the toxicity to cells also increased.

2) It is the inhibitory effect of dronedarone hydrochloride on the proliferation of esophageal squamous cell carcinoma cells (see Figure 2). Among them, when the concentration of dronedarone hydrochloride is in the range of 0 μM-2.5 μM, dronedarone hydrochloride can inhibit the proliferation of esophageal squamous cell carcinoma cells. KYSE150 and KYSE450 can inhibit proliferation; and with the increase of drug concentration, the inhibition of cell proliferation is more obvious. Specifically, when the concentration of dronedarone hydrochloride was 1 μM~2.5 μM, the proliferation inhibition of esophageal squamous cell carcinoma cell lines KYSE150 and KYSE450 was significant after 72 hours of culture, *p<0.05, **p<0.01, *** p<0.001.

3) is the toxic effect of dronedarone hydrochloride on gastric cancer cells (see Figure 3), among which, when dronedarone hydrochloride is in the concentration range of 3.125 μM-50 μM, dronedarone hydrochloride has an effect on esophageal squamous cell carcinoma cell lines HGC27 and AGS. Toxicity inhibition; with the increase of the concentration, the stronger the toxicity of dronedarone hydrochloride on gastric cancer cells.

4) is the inhibitory effect of dronedarone hydrochloride on the proliferation of gastric cancer cells (see Figure 4), wherein, when dronedarone hydrochloride is in the concentration range of 0 μM-2.5 μM, dronedarone hydrochloride can inhibit the production of HGC27 and AGS in gastric cell lines. Inhibition of proliferation; and with the increase of drug concentration, the inhibition of cell proliferation is more obvious. Specifically, when the concentration of dronedarone hydrochloride is 1 μM~2.5 μM, it has a significant inhibitory effect on the proliferation of gastric cancer cells HGC27 and AGS after 72 hours of culture, *p<0.05, **p<0.01, ***p<0.001 .

5) It is the effect of dronedarone hydrochloride on the colony formation of esophageal squamous cell carcinoma cells (see Figure 5). When the concentration of dronedarone hydrochloride is in the range of 0 μM to 2.5 μM, the effect of dronedarone hydrochloride on esophageal squamous cell carcinoma cell lines. With the increase of drug concentration, the number of clones of KYSE150 and KYSE450 decreased significantly, and the clones became significantly smaller; the figure shows the microscope photos and statistical results of clones with different concentrations. *p<0.05, **p<0.01, ***p<0.001. That is, dronedarone hydrochloride significantly inhibited the number of KYSE150 clones at a concentration of 1 μM to 2.5 μM, and significantly inhibited the number of KYSE450 clones at a concentration of 1.5 μM to 2.5 μM.

6) It is the growth inhibitory effect of dronedarone hydrochloride on the xenograft model of esophageal cancer human tumor (see Figure 6), wherein the mice treated with dronedarone hydrochloride had no significant change in body weight compared with the control, indicating that Dronedarone hydrochloride had no obvious toxic and side effects on mice, but the tumor size, weight and tumor volume of mice in the low-dose and high-dose groups treated with dronedarone hydrochloride were significantly decreased, indicating that dronedarone hydrochloride Good inhibitory effect of darone on tumor. Specifically, the low-dose group (30 mg/kg) and the high-dose group (120 mg/kg) of dronedarone hydrochloride had significant inhibitory effects on tumor volume and tumor weight, *p<0.05, **p<0.01 , ***p<0.001, therefore, dronedarone hydrochloride at the concentration of 30 mg/kg/day-120 mg/kg/day can inhibit the growth of mouse tumors in the human-derived esophageal squamous cell carcinoma xenograft model.

The above examples are only used to illustrate the preferred embodiments of the present invention, but the present invention is not limited to the above-mentioned embodiments, and any modifications made within the spirit and principles of the present invention within the scope of knowledge possessed by those of ordinary skill in the art , equivalent substitutions and improvements, etc., shall be regarded as the protection scope of this application.

Claims (9)

1. The application of dronedarone hydrochloride in preparing the medicine for resisting digestive tract tumors is characterized in that the anti-tumor medicine is a medicine for treating esophageal cancer or gastric cancer.

2. The use as claimed in claim 1 wherein the use of dronedarone hydrochloride for the manufacture of a medicament for the inhibition of the growth and transformation of esophageal squamous carcinoma cells.

3. The use according to claim 2, wherein dronedarone hydrochloride is capable of inhibiting the proliferation of esophageal squamous carcinoma cells and the number and size of colony formation at a concentration of 1 μ M to 2.5 μ M.

4. The use as claimed in claim 3 wherein the esophageal squamous cancer cells are KYSE150 cells and/or KYSE450 cells.

5. The use as claimed in claim 1 wherein the use of dronedarone hydrochloride for the manufacture of a medicament for inhibiting the growth and transformation of gastric cancer cells.

6. The use according to claim 5, wherein dronedarone hydrochloride is capable of inhibiting the proliferation and transformation of gastric cancer cells at a concentration of 1 μ M to 2.5 μ M.

7. The use according to claim 6, wherein the gastric cancer cells are HGC27 cells and/or AGS cells.

8. The use as claimed in claim 1 wherein the use of dronedarone hydrochloride for the manufacture of a medicament for inhibiting the growth of mouse tumours in a human model of oesophageal squamous carcinoma transplantable tumours.

9. The use as claimed in claim 8 wherein dronedarone hydrochloride is capable of inhibiting the growth of mouse tumours in a human derived oesophageal squamous carcinoma graft tumour model at a concentration of 30 mg/kg/day to 120 mg/kg/day.

Images