槲皮素激活焦亡途径抑制胃癌细胞增殖和迁移的机制研究  

Mechanism of quercetin activating the pyrolysis pathway to inhibit the proliferation and migration of gastric cancer cells

作　　者：荣耀 刘松华 唐明政 蔡辉 Yao Rong;Songhua Liu;Mingzheng Tang;Hui Cai(First School of Clinical Medical,Gansu University of Chinese Medicine,Lanzhou 730000,China;Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province,Lanzhou 730000,China;General Surgery Clinical Medical Center,Gansu Provincial Hospital,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学第一临床医学院,兰州市730000 [2]甘肃省外科肿瘤分子诊断与精准治疗重点实验室 [3]甘肃省人民医院普外临床中心

出　　处：《中国肿瘤临床》2023年第20期1033-1039,共7页Chinese Journal of Clinical Oncology

基　　金：甘肃省省委组织部甘肃重点人才项目(编号:2020RCXM076);2021年度中央引导地方科技发展资金支持项目(编号:ZYYDDFFZZJ-1);甘肃省优秀研究生“创新之星”项目(编号:2022CXZX748)资助。

摘　　要：目的:探讨槲皮素介导焦亡途径来发挥抗胃癌作用的机制。方法:将胃癌细胞分为实验组和经槲皮素干预的对照组。CCK-8实验检测槲皮素对AGS胃癌细胞增殖的影响;细胞划痕实验检测槲皮素对胃癌细胞迁移能力的影响。蛋白印记检测(Western blot)检测槲皮素干预后AGS细胞内裂解的半胱天冬酶1(cleaved caspase-1,CASP1)、加斯德明D(gasdermin D,GSDMD)等蛋白表达差异;构建敲减半胱天冬酶3(caspase-3,CASP3)基因的AGS稳转细胞株,并检测转染效率。Western blot检测AGS与AGS(shCASP3)中GSDMD、GSDME等蛋白表达差异。经槲皮素干预后,Western blot再次检测AGS(shCASP3)内GSDMD和加斯德明E(GSDME)等蛋白表达变化。结果:体外实验表明,槲皮素对AGS细胞的增殖和迁移能力有显著抑制作用,并能上调CASP1、GSDMD等蛋白的表达。与正常AGS细胞相比,AGS(shCASP3)细胞内GSDME表达上调,经各浓度槲皮素干预培养后,AGS(shCASP3)细胞内GSDME表达趋势逆转。结论:槲皮素能够抑制胃癌细胞增殖和迁移能力,这可能与槲皮素激活CASP1/GSDMD、CASP3/GSDME信号通路进而触发焦亡途径有关。Objective:The inhibitory mechanism of the quercetin-mediated pyroptosis pathway on gastric cancer cells was investigated.Methods:AGS gastric cancer cells were treated with quercetin(experimental group)or remained untreated(control group).The effect of quercetin on proliferation and migration was analyzed using the CCK-8 and cell scratch assays,respectively.Western blot was used to detect the differences in the expression levels of cleaved caspase-1(CASP1)and gasdermin D(GSDMD)in AGS cells after quercetin intervention.A CASP3-knockdown AGS stable cell line,AGS(shCASP3),was generated and the transfection efficiency was measured.Differences in the expressions of GSDMD and GSDME were determined by Western blot in normal AGS and AGS(shCASP3)cells after quercetin intervention.Results:Quercetin had a significant inhibitory effect on the proliferation and migration of AGS cells,and upregulated the expression levels of CASP1 and GSDMD proteins.Compared with normal AGS cells,GSDME protein was upregulated in AGS(shCASP3)cells,which was reversed after the intervention with quercetin.Conclusions:Quercetin inhibited the proliferation and migration of AGS gastric cancer cells.The effects may be related to the activation of the CASP1/GSDMD and CASP3/GSDME signaling pathways,which in turn trigger the pyroptosis pathways.

关 键 词：槲皮素 胃癌 焦亡 加斯德明D 半胱天冬酶3 

分 类 号：R735.2[医药卫生—肿瘤]