二甲双胍靶向IFIT2抑制肺癌细胞生长的机制研究
首发时间:2021-01-19
摘要:目的:二甲双胍是治疗2型糖尿病的一线降糖药物。近年来其在抗肿瘤治疗方面展现出的巨大潜力。本研究目的是探究二甲双胍对肺癌细胞的抗肿瘤机制,并确证IFIT2是二甲双胍治疗肺癌的作用靶点。方法:不同浓度二甲双胍(0,5,10,20,40,60,80,100mM)作用于烟致恶性转化细胞S30和肺癌细胞A549/H1299。CCK8法检测细胞活力,筛选出合适的二甲双胍干预浓度;二甲双胍干预后,LIVE/DEAD实验检测细胞存活率;流式细胞术检测细胞凋亡率;Transwell实验检测细胞迁移能力;实时荧光定量PCR(qRT-PCR)技术检测细胞中IFIT2的mRNA表达水平;Western blot检测IFIT2蛋白表达情况。使用si-IFIT2下调IFIT2表达同时用二甲双胍干预的挽救实验,采用划痕实验和克隆形成实验分析细胞迁移能力和克隆形成能力变化。结果:二甲双胍对肺癌相关细胞S30/A549/H1299的增殖具有抑制作用,其对三种细胞的IC50分别为53.995、36.649、57.787mM。二甲双胍干预后,IFIT2蛋白表达上调,细胞的增殖能力和迁移能力减弱,凋亡率增加。挽救实验结果表明siRNA-IFIT2对细胞迁移、克隆形成能力的促进作用可被二甲双胍所扭转。结论:二甲双胍可通过上调IFIT2蛋白表达,抑制肺癌细胞的增殖、迁移能力,促进肺癌细胞凋亡,从而发挥抗肿瘤效果,提示IFIT2有可能是二甲双胍发挥抗肿瘤作用的重要作用靶点。
关键词: 二甲双胍、IFIT2、肺癌
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Mechanism of metformin targeting IFIT2 to inhibit lung cancer cell growth
Abstract:Objective: Metformin is a first-line hypoglycemic agent for the treatment of type 2 diabetes. In recent years, it has shown great potential in anti-tumor therapy. The study is to explore the anti-tumor mechanism of metformin on lung cancer cells and confirm that IFIT2 is the target of metformin in the treatment of lung cancer. Methods:Different concentrations of metformin (0,5,10,20,40,60,80,100mM) added intoSmoke-induced malignant transformed cellsS30and lung cancer cells A549/H1299. CCK8 was used todetect cell viability to select the appropriate concentration of metformin; After metformin intervention, LIVE/DEAD experiment was used to detect cell survival; Flow cytometry was used totest the cell apoptosis rate; Transwell experiment was performed toanalyze cell migration ability; Real-time quantitative PCR (qRT-PCR) was used to detect IFIT2 mRNA expression level in cells; Western blot was used to detect IFIT2 protein expression. The rescue experiment in which si-IFIT2 was transfected to down-regulate the expression of IFIT2 and metformin was added to analyze the changes in cell migration ability and clonal formation ability by wound healing and clone formation experiment. Results: Metformin has an inhibitory effect on the proliferation of lung cancer-related cells S30/A549/H1299, and its IC50 for the three types of cells are 53.995, 36.649, 57.787mM, respectively. After the intervention of metformin, the expression of IFIT2 protein was up-regulated, the cell proliferation and migration ability decreased, and the apoptosis rate increased. The results of the rescue experiment showed that the promotion effect of siRNA-IFIT2 on cell migration and clonal formation could be reversed by metformin. Conclusion: Metformin can up-regulate the expression of IFIT2 protein, inhibit the proliferation and migration of lung cancer cells, and promote lung cancer cell apoptosis, thereby exerting an anti-tumor effect. IFIT2 is an important target for metformin to exert its anti-tumor effect.
Keywords: Metformin IFIT2 Lung cancer
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二甲双胍靶向IFIT2抑制肺癌细胞生长的机制研究
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