二甲双胍联合吉西他滨对胰腺癌细胞增殖、迁移及上皮间质转化的影响  

Effects of metformin combined with gemcitabine on proliferation,migration,and epithelial-mesenchymal transition of pancreatic cancer cells

作　　者：王文婷[1] 彭钊[1] 邓祖亮[1] 周轩 刘力[1] WANG Wenting;PENG Zhao;DENG Zuliang;ZHOU Xuan;LIU Li(The Affiliated Hospital of Xiangnan University,Chenzhou 423000,China)

机构地区：[1]湘南学院附属医院,湖南郴州423000

出　　处：《山东医药》2021年第10期41-44,共4页Shandong Medical Journal

基　　金：郴州市重点研发及技术创新专项资金医卫类和校企合作类项目(zdyf201972)。

摘　　要：目的探讨二甲双胍联合吉西他滨对胰腺癌细胞增殖、迁移及上皮间质转化的影响。方法选择胰腺癌PANC-1细胞,常规传代培养,采用MTT法检测终浓度为0、5、10、20、40 mmol/L二甲双胍或终浓度为0、0.1、0.2、0.4、0.8μmol/L吉西他滨干预时细胞增殖活性,以能够使细胞增殖活性降至50%左右时的二甲双胍和吉西他滨浓度进行后续实验。另取PANC-1细胞,随机分为正常对照组、二甲双胍组、吉西他滨组、联合用药组,分别给予相应浓度的二甲双胍或(和)吉西他滨干预,采用细胞划痕实验检测细胞迁移率,采用Western blotting法检测上皮型钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)表达。结果随着二甲双胍、吉西他滨浓度升高,PANC-1细胞增殖活性逐渐降低,呈浓度依赖性(F分别为29.14、66.88,P均<0.01)。20 mmol/L二甲双胍或0.4μmol/L吉西他滨干预时,PANC-1细胞增殖活性降至50%左右,故以20 mmol/L二甲双胍和0.4μmol/L吉西他滨进行后续实验。二甲双胍组、吉西他滨组、联合用药组细胞迁移率及E-cadherin、Vimentin蛋白相对表达量均低于正常对照组,联合用药组细胞迁移率及E-cadherin、Vimentin蛋白相对表达量均低于二甲双胍组、吉西他滨组(P均<0.05)。而二甲双胍组与吉西他滨组细胞迁移率及E-cadherin、Vimentin蛋白相对表达量比较差异均无统计学意义(P均>0.05)。结论二甲双胍联合吉西他滨能够抑制胰腺癌细胞增殖、迁移及上皮间质转化;二甲双胍能够提高胰腺癌细胞对吉西他滨的化疗敏感性。Objective To investigate the effects of metformin combined with gemcitabine on the proliferation,migra⁃tion,and epithelial-mesenchymal transition(EMT)of pancreatic cancer cells.Methods The pancreatic cancer PANC-1 cells were selected and subcultured.The cell proliferation activity was measured by MTT assay when the final metformin concentrations were 0,5,10,20,40 mmol/L or the final gemcitabine concentrations were 0,0.1,0.2,0.4,0.8μmol/L,and the follow-up experiments were carried out with the concentrations of metformin and gemcitabine that could reduce the cell proliferation activity to about 50%.Besides,PANC-1 cells were selected again and were randomly divided into three groups:the control group,metformin group,gemcitabine group,and combination group.The cells were treated with met⁃formin or/and gemcitabine.The cell migration rate was measured by cell scratch assay.The expression levels of E-cad⁃herin and Vimentin was detected by Western blotting.Results The proliferation activity of PANC-1 cells decreased with the increased concentrations of metformin and gemcitabine,in a concentration-dependent manner(F=29.14,66.88,both P<0.01).After giving metformin(20 mmol/L)and gemcitabine(0.4μmol/L),the proliferation activity of PANC-1 cells decreased to about 50%,so the follow-up experiments were conducted with these concentrations.The cell migration rates and the expression levels of E-cadherin and Vimentin in the metformin group,gemcitabine group,and combination group were lower than those in the control group;the cell migration rate and the expression levels of E-cadherin and Vimentin in the combination group were lower than those in the metformin and gemcitabine groups(all P<0.05).There was no significant difference in the cell migration rate or expression levels of E-cadherin and Vimentin between the metformin group and gemcitabine group(all P>0.05).Conclusion The combination therapy of metformin and gemcitabine can inhibit the proliferation,migration and EMT of pancreatic cancer cells,and metformin improve

关 键 词：胰腺癌 二甲双胍 吉西他滨 细胞增殖 细胞迁移 上皮间质转化 

分 类 号：R735.9[医药卫生—肿瘤]