CN115804776A - Application of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in combination in tumor treatment and inhibition drugs - Google Patents
Application of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in combination in tumor treatment and inhibition drugs Download PDFInfo
- Publication number
- CN115804776A CN115804776A CN202211620904.5A CN202211620904A CN115804776A CN 115804776 A CN115804776 A CN 115804776A CN 202211620904 A CN202211620904 A CN 202211620904A CN 115804776 A CN115804776 A CN 115804776A
- Authority
- CN
- China
- Prior art keywords
- fluorouracil
- aromatic hydrocarbon
- hydrocarbon receptor
- receptor inhibitor
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 229960002949 fluorouracil Drugs 0.000 title claims abstract description 43
- 150000004945 aromatic hydrocarbons Chemical class 0.000 title claims abstract description 22
- 108091006082 receptor inhibitors Proteins 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 title claims abstract description 15
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 10
- 230000005764 inhibitory process Effects 0.000 title abstract description 4
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 28
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 25
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 6
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 37
- BGFHMYJZJZLMHW-UHFFFAOYSA-N 4-[2-[[2-(1-benzothiophen-3-yl)-9-propan-2-ylpurin-6-yl]amino]ethyl]phenol Chemical group N1=C(C=2C3=CC=CC=C3SC=2)N=C2N(C(C)C)C=NC2=C1NCCC1=CC=C(O)C=C1 BGFHMYJZJZLMHW-UHFFFAOYSA-N 0.000 claims description 31
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims description 6
- 210000004881 tumor cell Anatomy 0.000 claims description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 claims description 5
- 239000002609 medium Substances 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 3
- 229930182555 Penicillin Natural products 0.000 claims description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 3
- 239000012091 fetal bovine serum Substances 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 229940049954 penicillin Drugs 0.000 claims description 3
- 229960005322 streptomycin Drugs 0.000 claims description 3
- 230000035755 proliferation Effects 0.000 abstract description 12
- 230000002195 synergetic effect Effects 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 abstract description 3
- 239000002547 new drug Substances 0.000 abstract 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 11
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 10
- YGPSJZOEDVAXAB-UHFFFAOYSA-N kynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 description 8
- 102000003984 Aryl Hydrocarbon Receptors Human genes 0.000 description 7
- 108090000448 Aryl Hydrocarbon Receptors Proteins 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 5
- RSTKLPZEZYGQPY-UHFFFAOYSA-N 3-(indol-3-yl)pyruvic acid Chemical compound C1=CC=C2C(CC(=O)C(=O)O)=CNC2=C1 RSTKLPZEZYGQPY-UHFFFAOYSA-N 0.000 description 2
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 2
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 2
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 2
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 101150108435 GLK1 gene Proteins 0.000 description 1
- 101000926525 Homo sapiens eIF-2-alpha kinase GCN2 Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000001892 Protein Kinase C-theta Human genes 0.000 description 1
- 108010015499 Protein Kinase C-theta Proteins 0.000 description 1
- 230000033540 T cell apoptotic process Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
- 230000010632 Transcription Factor Activity Effects 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 101100229372 Trypanosoma brucei brucei GK gene Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 102100034175 eIF-2-alpha kinase GCN2 Human genes 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000015909 regulation of biological process Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
技术领域technical field
本发明属于制药领域，涉及一种芳香烃受体抑制剂和5-氟尿嘧啶合用在治疗抑制肿瘤药物中的应用。合用芳香烃受体抑制剂和5-氟尿嘧啶抑制肿瘤细胞的增殖，芳香烃受体抑制剂SR1和5-氟尿嘧啶联合使用在治疗结肠癌药物中的应用。The invention belongs to the field of pharmacy, and relates to the combined use of an aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in treating and suppressing tumor drugs. Combined use of an aromatic hydrocarbon receptor inhibitor and 5-fluorouracil to inhibit the proliferation of tumor cells, and the combined use of an aromatic hydrocarbon receptor inhibitor SR1 and 5-fluorouracil in the treatment of colon cancer drugs.
技术背景technical background
色氨酸是人体必须氨基酸之一，参与蛋白质合成和代谢调节。色氨酸在体内有四条代谢途径：一是在羟化酶的作用下生成5-羟色胺，二是经脱羧基作用生成色胺，三是经转氨基作用生成吲哚丙酮酸，四是经犬尿氨酸代谢途径生成犬尿氨酸等多种代谢产物。其中，约95%的色氨酸经过犬尿氨酸通路进行代谢。Tryptophan is one of the essential amino acids for the human body, involved in protein synthesis and metabolic regulation. Tryptophan has four metabolic pathways in the body: one is to generate 5-hydroxytryptamine under the action of hydroxylase, the other is to generate tryptophan through decarboxylation, the third is to generate indolepyruvate through transamination, and the fourth is to generate The urine metabolic pathway produces kynurenine and other metabolites. Among them, about 95% of tryptophan is metabolized through the kynurenine pathway.
近年来研究发现，色氨酸代谢主要通过其分解代谢导致色氨酸耗竭和代谢产物的积聚影响肿瘤发生发展。肿瘤细胞通过分泌γ-干扰素诱导IDO1高表达， IDO1高表达加速色氨酸代谢，导致肿瘤微环境中色氨酸浓度的下降。色氨酸耗竭不但可以增加胞内未负载tRNA水平，激活压力应答激酶GCN2，从而抑制T细胞中蛋白质的翻译过程，参与免疫调控；色氨酸耗竭也可以通过阻断氨基酸感应激酶GLK1，抑制雷帕霉素靶蛋白mTOR和T细胞受体调节激酶PKC-Θ，诱导自噬的发生。In recent years, studies have found that tryptophan metabolism mainly affects the development of tumors through its catabolism leading to tryptophan depletion and accumulation of metabolites. Tumor cells induce the high expression of IDO1 by secreting γ-interferon, and the high expression of IDO1 accelerates the metabolism of tryptophan, resulting in a decrease in the concentration of tryptophan in the tumor microenvironment. Tryptophan depletion can not only increase the level of intracellular unloaded tRNA, but also activate the stress-responsive kinase GCN2, thereby inhibiting the translation process of proteins in T cells and participating in immune regulation; tryptophan depletion can also block the amino acid-sensitive kinase GLK1, inhibit the The pamycin target protein mTOR and the T-cell receptor-regulated kinase PKC-Θ induce autophagy.
色氨酸代谢产物均被报道可以抑制T细胞功能，诱导T细胞凋亡，其中以犬尿氨酸参与肿瘤免疫逃逸的相关机制研究最为深入。芳香烃受体是一种重要的配体激活转录因子，参与调控细胞周期、免疫应答和细胞分化等生物学过程，在胚胎发育和肿瘤发生中发挥关键作用。犬尿氨酸是芳香烃受体的内源性配体，与芳香烃受体结合后，激活其转录因子活性，调控下游靶基因的表达。犬尿氨酸-芳香烃受体信号的活化促进FoxP3+ Treg细胞分化，伴随IL-6、IL-10等炎性因子分泌增加，促进肿瘤细胞的生长。目前认为，芳香烃受体在肿瘤的发生发展过程中通过多种途径发挥作用，芳香烃受体是肿瘤治疗的潜在靶点。Tryptophan metabolites have been reported to inhibit T cell function and induce T cell apoptosis, among which the mechanism of kynurenine participating in tumor immune escape is the most in-depth study. Aryl hydrocarbon receptor is an important ligand-activated transcription factor, which is involved in the regulation of biological processes such as cell cycle, immune response and cell differentiation, and plays a key role in embryonic development and tumorigenesis. Kynurenine is the endogenous ligand of the aryl hydrocarbon receptor. After binding to the aryl hydrocarbon receptor, it activates its transcription factor activity and regulates the expression of downstream target genes. The activation of kynurenine-aryl hydrocarbon receptor signaling promotes the differentiation of FoxP3 + Treg cells, accompanied by the increased secretion of inflammatory factors such as IL-6 and IL-10, and promotes the growth of tumor cells. At present, it is believed that aryl hydrocarbon receptors play a role in various ways in the process of tumor development, and aryl hydrocarbon receptors are potential targets for tumor therapy.
结直肠癌是常见的消化道恶性疾病，全球范围内其死亡率高居第三位。5-氟尿嘧啶作为抗代谢抗肿瘤药物，是治疗晚期结直肠癌患者的一线用药。然而，临床治疗过程中产生的化学耐受性严重限制了药物疗效。因此，发明人提出芳香烃受体抑制剂抑制剂SR1（Stem Regenin 1）与5-氟尿嘧啶联用可增强药物敏感性，提高临床疗效。Colorectal cancer is a common malignant disease of the digestive tract, and its mortality rate ranks third in the world. 5-Fluorouracil, as an antimetabolite and antineoplastic drug, is the first-line drug for the treatment of patients with advanced colorectal cancer. However, chemoresistance developed during clinical treatment severely limits drug efficacy. Therefore, the inventors propose that the combined use of the aromatic hydrocarbon receptor inhibitor SR1 (Stem Regenin 1) and 5-fluorouracil can enhance drug sensitivity and improve clinical efficacy.
发明内容Contents of the invention
本发明目的在于提供一种芳香烃受体抑制剂和5-氟尿嘧啶合用在治疗抑制肿瘤药物中的应用。The purpose of the present invention is to provide a combined application of an aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in treating and suppressing tumor drugs.
本发明目的提供以下方案实现：一种芳香烃受体抑制剂和5-氟尿嘧啶合用在治疗抑制肿瘤药物中的应用，通过合用芳香烃受体抑制剂和5-氟尿嘧啶抑制肿瘤细胞的增殖。The purpose of the present invention is to provide the following solution: a combination of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in the treatment of anti-tumor drugs, through the combination of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil to inhibit the proliferation of tumor cells.
所述芳香烃受体抑制剂为Stem Regenin 1（SR1）。The aromatic hydrocarbon receptor inhibitor is Stem Regenin 1 (SR1).
优选的，所述SR1与5-氟尿嘧啶的质量比为1:2。Preferably, the mass ratio of SR1 to 5-fluorouracil is 1:2.
所述肿瘤细胞为结肠癌细胞。The tumor cells are colon cancer cells.
本发明通过试验证明，SR1与5-氟尿嘧啶联合使用对人原发性结肠癌细胞系的增殖发挥了协同抑制作用，包括SW620和HCT116结肠癌细胞。因此，5-氟尿嘧啶和芳香烃受体抑制剂SR1联合使用在结肠癌的药物治疗中具有广阔的应用前景。The present invention proves through experiments that the combined use of SR1 and 5-fluorouracil exerts a synergistic inhibitory effect on the proliferation of human primary colon cancer cell lines, including SW620 and HCT116 colon cancer cells. Therefore, the combined use of 5-fluorouracil and the aromatic hydrocarbon receptor inhibitor SR1 has broad application prospects in the drug treatment of colon cancer.
附图说明Description of drawings
附图1 给药7天后各组对SW620细胞的增殖抑制率；Accompanying drawing 1 The proliferation inhibition rate of each group to SW620 cell after 7 days of administration;
附图2 给药7天后各组对HCT116细胞的增殖抑制率。Figure 2 The growth inhibition rate of HCT116 cells in each group after 7 days of administration.
如图所示，单独使用5-氟尿嘧啶和芳香烃受体抑制剂SR1均能在一定程度上抑制结肠癌细胞的增殖，将10μM 5-氟尿嘧啶和5μM SR1联合使用对SW620和HCT116细胞增殖的抑制作用均显著增强，取得了协同增效的效果。As shown in the figure, the single use of 5-fluorouracil and the aromatic hydrocarbon receptor inhibitor SR1 can inhibit the proliferation of colon cancer cells to a certain extent, and the combined use of 10 μM 5-fluorouracil and 5 μM SR1 can inhibit the proliferation of SW620 and HCT116 cells Both were significantly enhanced, achieving a synergistic effect.
具体实施方式Detailed ways
本发明通过下面的实施例进行详细解释，但不仅限于此。The present invention is explained in detail by the following examples, but is not limited thereto.
实施例1Example 1
一种芳香烃受体抑制剂SR1和5-氟尿嘧啶合用在治疗抑制人原发性结肠癌细胞系SW620药物中的应用：A combination of aryl hydrocarbon receptor inhibitor SR1 and 5-fluorouracil in the treatment of drugs that inhibit human primary colon cancer cell line SW620:
细胞来源与培养：人原发性结肠癌细胞系SW620购于上海中科院细胞库，细胞采用含10%胎牛血清、100U/ml青霉素和100μg/ml链霉素的DMEM培养基培养于37℃、5%CO2培养箱中。Cell source and culture: The human primary colon cancer cell line SW620 was purchased from the Cell Bank of the Chinese Academy of Sciences in Shanghai. The cells were cultured in DMEM medium containing 10% fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin at 37°C. 5% CO2 incubator.
实验方法：采用CCK8实验方法检测SR1与5-氟尿嘧啶联合使用对结肠癌细胞生长的影响。具体操作如下：SW620细胞以800个细胞/孔的密度接种于96孔板中培养；将细胞分为4组：Experimental method: CCK8 experimental method was used to detect the effect of SR1 combined with 5-fluorouracil on the growth of colon cancer cells. The specific operation is as follows: SW620 cells were seeded in a 96-well plate at a density of 800 cells/well and cultured; the cells were divided into 4 groups:
1）单独使用5-氟尿嘧啶组，剂量为10μM；1) The 5-fluorouracil group was used alone, with a dose of 10 μM;
2)单独使用SR1组，剂量为5μM；2) The SR1 group was used alone, with a dose of 5 μM;
3)5-氟尿嘧啶和SR1联合使用组，5-氟尿嘧啶的剂量为10μM，SR1的剂量为5μM；3) In the combined use group of 5-fluorouracil and SR1, the dose of 5-fluorouracil is 10 μM, and the dose of SR1 is 5 μM;
4）对照组，为不加药的DMEM培养基组。4) The control group is the DMEM medium group without drugs.
加药后，各组培养基每48小时更换一次，培养7天后使用酶标仪检测。After dosing, the culture medium of each group was replaced every 48 hours, and detected with a microplate reader after 7 days of culture.
结果如图1所示，单独使用5-氟尿嘧啶和芳香烃受体抑制剂SR1均能在一定程度上抑制结肠癌细胞的增殖，将10μM 5-氟尿嘧啶和5μM SR1联合使用对结肠癌细胞增殖的抑制作用均显著增强，取得了协同增效的效果。The results are shown in Figure 1. Both 5-fluorouracil and the aromatic hydrocarbon receptor inhibitor SR1 alone can inhibit the proliferation of colon cancer cells to a certain extent, and the combined use of 10 μM 5-fluorouracil and 5 μM SR1 can inhibit the proliferation of colon cancer cells The effects were significantly enhanced, and a synergistic effect was obtained.
实施例2Example 2
芳香烃受体抑制剂SR1和5-氟尿嘧啶合用在治疗抑制人原发性结肠癌细胞系HCT116药物中的应用，Combination of aryl hydrocarbon receptor inhibitor SR1 and 5-fluorouracil in the treatment of drugs that inhibit human primary colon cancer cell line HCT116,
细胞来源与培养：人原发性结肠癌细胞系HCT116购于上海中科院细胞库，细胞采用含10%胎牛血清、100U/ml青霉素和100μg/ml链霉素的DMEM培养基培养于37℃、5%CO2培养箱中；Cell source and culture: The human primary colon cancer cell line HCT116 was purchased from the Cell Bank of the Chinese Academy of Sciences in Shanghai. The cells were cultured in DMEM medium containing 10% fetal bovine serum, 100 U/ml penicillin and 100 μg/ml streptomycin at 37°C, 5% CO2 incubator;
实验方法：采用CCK8实验方法检测SR1与5-氟尿嘧啶联合使用对结肠癌细胞生长的影响。具体操作如下：HCT116细胞以800个细胞/孔的密度接种于96孔板中培养，将细胞分为4组：Experimental method: CCK8 experimental method was used to detect the effect of SR1 combined with 5-fluorouracil on the growth of colon cancer cells. The specific operation is as follows: HCT116 cells were cultured in a 96-well plate at a density of 800 cells/well, and the cells were divided into 4 groups:
1）单独使用5-氟尿嘧啶组，5-氟尿嘧啶的剂量为10μM；1) The 5-fluorouracil group was used alone, and the dose of 5-fluorouracil was 10 μM;
2）单独使用SR1组，SR1的剂量为5μM；2) The SR1 group was used alone, and the dose of SR1 was 5 μM;
3）5-氟尿嘧啶和SR1联合使用组，5-氟尿嘧啶的剂量为10μM，SR1的剂量为5μM；3) In the combined use group of 5-fluorouracil and SR1, the dose of 5-fluorouracil was 10 μM, and the dose of SR1 was 5 μM;
4）对照组，为不加药的DMEM培养基组。4) The control group is the DMEM medium group without drugs.
加药后，各组培养基每48小时更换一次，培养7天后使用酶标仪检测。After dosing, the culture medium of each group was replaced every 48 hours, and detected with a microplate reader after 7 days of culture.
结果如图2所示，单独使用5-氟尿嘧啶和芳香烃受体抑制剂SR1均能在一定程度上抑制结肠癌细胞的增殖，将10μM 5-氟尿嘧啶和5μM SR1联合使用对结肠癌细胞增殖的抑制作用均显著增强，取得了协同增效的效果。The results are shown in Figure 2. Both 5-fluorouracil and the aromatic hydrocarbon receptor inhibitor SR1 alone can inhibit the proliferation of colon cancer cells to a certain extent, and the combined use of 10 μM 5-fluorouracil and 5 μM SR1 can inhibit the proliferation of colon cancer cells The effects were significantly enhanced, and a synergistic effect was obtained.
综上，本发明提供了一种治疗结肠癌的联合用药物。本发明首次发现，芳香烃受体抑制剂SR1与5-氟尿嘧啶联合使用对人原发性结肠癌细胞系的增殖发挥了协同抑制作用。因此，5-氟尿嘧啶和芳香烃受体抑制剂SR1联合使用在结肠癌的治疗药物中具有广阔的应用前景。In summary, the present invention provides a combination drug for treating colon cancer. The present invention finds for the first time that the combined use of the aromatic hydrocarbon receptor inhibitor SR1 and 5-fluorouracil exerts a synergistic inhibitory effect on the proliferation of human primary colon cancer cell lines. Therefore, the combined use of 5-fluorouracil and the aromatic hydrocarbon receptor inhibitor SR1 has broad application prospects in the treatment of colon cancer.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211620904.5A CN115804776A (en) | 2022-12-16 | 2022-12-16 | Application of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in combination in tumor treatment and inhibition drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211620904.5A CN115804776A (en) | 2022-12-16 | 2022-12-16 | Application of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in combination in tumor treatment and inhibition drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115804776A true CN115804776A (en) | 2023-03-17 |
Family
ID=85486030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211620904.5A Pending CN115804776A (en) | 2022-12-16 | 2022-12-16 | Application of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in combination in tumor treatment and inhibition drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115804776A (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1889969A (en) * | 2003-12-05 | 2007-01-03 | 新纪元公司 | Methods for treating prostate cancer with herbal compositions |
| WO2007089871A2 (en) * | 2006-02-01 | 2007-08-09 | The Johns Hopkins University | Polypeptide-nucleic acid conjugate for immunoprophylaxis or immunotherapy for neoplastic or infectious disorders |
| US20100331250A1 (en) * | 2009-03-18 | 2010-12-30 | Joe Zhou | Anti-angiogenesis fusion proteins |
| CN106581021A (en) * | 2016-11-17 | 2017-04-26 | 浙江省医学科学院 | Application of combination of atractyloside and 5-fluorouracil in preparation of medicine for prevention and therapy of rectal cancer |
| CN110831600A (en) * | 2017-04-21 | 2020-02-21 | 金恩医疗公司 | Indole AHR inhibitors and their uses |
| CN113301897A (en) * | 2018-10-17 | 2021-08-24 | 美真达治疗公司 | Methods of treating cancer with arene receptor antagonists |
| CN113874493A (en) * | 2019-03-28 | 2021-12-31 | 韩国生命工学研究院 | Method for producing CAR gene-introduced NK cells and use thereof |
| CN115381959A (en) * | 2022-09-30 | 2022-11-25 | 上海纳米技术及应用国家工程研究中心有限公司 | Combined medicine for treating liver cancer |
| CN115381836A (en) * | 2022-09-30 | 2022-11-25 | 上海纳米技术及应用国家工程研究中心有限公司 | Combination drug for treating lung cancer |
-
2022
- 2022-12-16 CN CN202211620904.5A patent/CN115804776A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1889969A (en) * | 2003-12-05 | 2007-01-03 | 新纪元公司 | Methods for treating prostate cancer with herbal compositions |
| WO2007089871A2 (en) * | 2006-02-01 | 2007-08-09 | The Johns Hopkins University | Polypeptide-nucleic acid conjugate for immunoprophylaxis or immunotherapy for neoplastic or infectious disorders |
| US20100331250A1 (en) * | 2009-03-18 | 2010-12-30 | Joe Zhou | Anti-angiogenesis fusion proteins |
| CN106581021A (en) * | 2016-11-17 | 2017-04-26 | 浙江省医学科学院 | Application of combination of atractyloside and 5-fluorouracil in preparation of medicine for prevention and therapy of rectal cancer |
| CN110831600A (en) * | 2017-04-21 | 2020-02-21 | 金恩医疗公司 | Indole AHR inhibitors and their uses |
| CN113301897A (en) * | 2018-10-17 | 2021-08-24 | 美真达治疗公司 | Methods of treating cancer with arene receptor antagonists |
| US20210379033A1 (en) * | 2018-10-17 | 2021-12-09 | Magenta Therapeutics Inc. | Methods of treating cancer with aryl hydrocarbon receptor antagonists |
| CN113874493A (en) * | 2019-03-28 | 2021-12-31 | 韩国生命工学研究院 | Method for producing CAR gene-introduced NK cells and use thereof |
| CN115381959A (en) * | 2022-09-30 | 2022-11-25 | 上海纳米技术及应用国家工程研究中心有限公司 | Combined medicine for treating liver cancer |
| CN115381836A (en) * | 2022-09-30 | 2022-11-25 | 上海纳米技术及应用国家工程研究中心有限公司 | Combination drug for treating lung cancer |
Non-Patent Citations (4)
| Title |
|---|
| GAUTAM, P: "Identification of selective cytotoxic and synthetic lethal drug responses in triple negative breast cancer cells", 《MOLECULAR CANCER》, no. 15, 10 May 2016 (2016-05-10), pages 1 - 16, XP002769732, DOI: 10.1186/s12943-016-0517-3 * |
| 何珩: "AHR与肿瘤发生发展相关性的研究进展", 《肿瘤预防与治疗》, vol. 30, no. 3, 25 June 2017 (2017-06-25), pages 226 - 231 * |
| 张彤: "《家庭常用药物手册》", 31 January 1998, 中央民族大学出版社, pages: 479 * |
| 王翠娟: "芳香烃受体在肿瘤发生及免疫治疗中的作用", 《中华肿瘤防治杂志》, vol. 25, no. 15, 14 August 2018 (2018-08-14), pages 1126 - 1130 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107801379A (en) | anticancer agent | |
| JP7302025B2 (en) | Use of FGF21 in the manufacture of a drug for treating colorectal cancer | |
| Wang et al. | Targeting cancer cachexia: Molecular mechanisms and clinical study | |
| Huang et al. | Rutaecarpine alleviates acute pancreatitis in mice and AR42J cells by suppressing the MAPK and NF‐κB signaling pathways via calcitonin gene‐related peptide | |
| Liang et al. | Targeting metabolism to enhance immunotherapy within tumor microenvironment | |
| CN104758292B (en) | PD-0332991 is preparing the purposes of prevention drug-resistant tumor drug | |
| Zhang et al. | Kaempferol 3‐O‐gentiobioside, an ALK5 inhibitor, affects the proliferation, migration, and invasion of tumor cells via blockade of the TGF‐β/ALK5/Smad signaling pathway | |
| CN114870009A (en) | Anti-tumor combined composition, application thereof and anti-tumor medicine | |
| Huang et al. | Trifolirhizin reduces osteoclast formation and prevents inflammatory osteolysis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signaling pathways and ROS | |
| CN114469950A (en) | Application of chelidonine in preparation of FLT3-ITD mutant acute myelogenous leukemia treatment drug | |
| Zhang et al. | Pirfenidone antagonizes TGF-β1-mediated gabapentin resistance via reversal of desmoplasia and the ‘cold’microenvironment in pancreatic cancer | |
| CN115804776A (en) | Application of aromatic hydrocarbon receptor inhibitor and 5-fluorouracil in combination in tumor treatment and inhibition drugs | |
| CN110664818B (en) | A drug to treat lung cancer | |
| CN115381959A (en) | Combined medicine for treating liver cancer | |
| KR20140144215A (en) | Methods of treating cancer using aurora kinase inhibitors | |
| CN115381836A (en) | Combination drug for treating lung cancer | |
| CN108403690A (en) | It is a kind of inhibit melanoma cells proliferation drug and its application | |
| Wang et al. | Therapeutic targeting of cGAS–STING pathway in lung cancer | |
| JP7483699B2 (en) | Supernatants from co-cultures of macrophages with irradiated leukocytes for controlling tumor progression or restoring antitumor immunity | |
| CN105769863A (en) | Application of tipranavir in anticancer drugs and anticancer drugs | |
| CN106333951B (en) | A kind of application of mTOR kinase inhibitors and the composition of mapk kinase inhibitor | |
| Zhang et al. | Emodin regulated lactate metabolism by inhibiting MCT1 to delay non-small cell lung cancer progression | |
| CN111803489A (en) | Application of michelia lactone and derivatives thereof in treatment of pituitary adenoma | |
| CN115887669A (en) | A pharmaceutical composition for treating cancer | |
| TWI813694B (en) | Antineoplastic agent and tumor treatment method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20230317 |
|
| RJ01 | Rejection of invention patent application after publication |