硫利达嗪协同二甲双胍对肺癌细胞的抑制作用及其机制  

The Synergistic Effect of Thiolidazine and Metformin on Lung Cancer Cells and its Mechanism

作　　者：王芳 刘星吟 王攀琦 刘洋 刘复兴 宁志丰 WANG Fang;LIU Xing-yin;NING Zhi-feng(School of Pharmacy,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院药学院,湖北咸宁437100 [2]湖北科技学院基础医学院

出　　处：《湖北科技学院学报（医学版）》2021年第5期388-392,共5页Journal of Hubei University of Science and Technology(Medical Sciences)

基　　金：2021年度咸宁市高层次人才择优资助项目[咸人社函(2021)7号];2020年度五官医学院专项科研基金项目(2)。

摘　　要：目的探讨硫利达嗪联合二甲双胍对肺癌的作用及机制。方法以人肺腺癌H1975细胞为研究对象,采用四甲基偶氮唑盐(MTT)法检测不同浓度硫利达嗪、二甲双胍在24、48h对H1975细胞增殖的作用;通过平板克隆形成实验检测两药对H1975细胞克隆形成能力的作用;通过Transwell小室方法检测两药对H1975细胞迁移、侵袭能力的影响;通过Western blot检测两药联用对p-Akt、p-PI3K、p-mTOR蛋白表达水平的影响。结果与对照组相比,单独使用硫利达嗪、二甲双胍和两药联用均能抑制H1975细胞的增殖、克隆形成、迁移、侵袭能力,且明显抑制p-Akt、p-PI3K、p-mTOR蛋白的表达,联合用药组比单药组效果更加显著,差异具有统计学意义(P<0.05),且联合指数CI<1,硫利达嗪与二甲双胍有协同增效作用。结论硫利达嗪协同增敏二甲双胍对肺癌细胞的抑制作用,与下调p-Akt、p-mTOR蛋白的表达有关。Objective To investigate the effect of thioridazine combined with metformin on lung cancer and its regulatory mechanism.Methods MTT assay was used to detect the effects of different concentrations of thioridazine and metformin on the proliferation of H1975 cells at 24h and 48h.The effects of thioridazine and metformin on the migration,invasion and cloning ability of H1975 cells were detected by the Transwell chamber method and plate clone formation experiment respectively.Western blot was used to detect the effects of the two drugs on the expression levels of p-Akt and p-mTOR.Results Compared with the control group,thioridazine,metformin and the combination of the two drugs could inhibit the proliferation,clone formation,migrationand invasion of H1975 cells,and significantly inhibited the protein expression of p-Akt,p-PI3K,and p-mTOR.The effect of the combination drug group was more significant than that of the single drug group,and the difference was statistically significant(P<0.05).The combination index CI<1among effects observed in experiments suggesting a significant synergistic effect between thioridazine and metformin.Conclusion hioridazine synergistically enhances the inhibitory effect of metformin on lung cancer cells,which is related to the down-regulation of the expression of p-Akt,p-mTOR protein.

关 键 词：肺癌 硫利达嗪 二甲双胍 AKT MTOR 

分 类 号：R734[医药卫生—肿瘤]