二甲双胍抑制人宫颈鳞癌细胞系SiHa和CaSKi增殖及促进细胞凋亡  

Metformin inhibits proliferation and promotes apoptosis of human cervical squamous cell carcinoma cell lines SiHa and CaSki

作　　者：刘婷婷[1] 韩超[1] 赵小玲 孔为民[1] LIU Tingting;HAN Chao;ZHAO Xiaoling;KONG Weimin(Department of Gynecological Oncology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital,Beijing 100006,China)

机构地区：[1]首都医科大学附属北京妇产医院/北京妇幼保健院妇科肿瘤科,北京100006

出　　处：《基础医学与临床》2023年第2期283-288,共6页Basic and Clinical Medicine

基　　金：首都医科大学附属北京妇产医院中青年学科骨干培养专项课题(FCYY201706)。

摘　　要：目的研究二甲双胍(Met)对宫颈鳞癌细胞增殖的影响及作用机制。方法CCK-8法检测人宫颈癌鳞癌细胞系SiHa和CaSKi的增殖,计算二甲双胍半抑制浓度(IC_(50))。流式细胞仪检测细胞周期及凋亡。Western blot检测腺苷酸活化蛋白激酶-哺乳动物雷帕霉素靶蛋白(AMPK-mTOR)信号通路相关蛋白表达。结果随着药物浓度增加、作用时间延长,细胞增殖率下降(P<0.05)。SiHa细胞48和72 h IC_(50)浓度分别为(50.95±2.63)和(21.39±5.23)mmol/L,CaSKi细胞48和72 h IC_(50)浓度分别为(9.98±1.63)和(7.47±2.09)mmol/L。Met组G_(2)/M期细胞含量减少,S期细胞含量增加(P<0.05)。Met组细胞凋亡率较对照组增加(P<0.05)。Met组磷酸化-AMPK(p-AMPK)表达量增加,磷酸化-S6K(p-S6K)、磷酸化-4E-BP1(p-4E-BP1)表达量减少(P<0.05)。结论二甲双胍抑制宫颈鳞癌细胞系增殖的作用可能与促进细胞凋亡、阻滞细胞周期于S期、激活AMPK-mTOR信号通路有关。Objective To investigate the effects and mechanism of metformin(Met)on the proliferation of cervical squamous cell carcinoma.Methods CCK-8 method was used to check the proliferation of cells lines SiHa and CaSKi,the semi inhibitory concentration of metformin(IC_(50))was calculated as well.The cell cycle and apoptosis were examined by flow cytometry,and the expression of AMPK-mTOR signal pathway related proteins was detected by Western blot.Results With the increase of drug concentration and time,the cell proliferation rate decreased(P<0.05).The IC_(50)concentrations of SiHa cells at 48 and 72 h were(50.95±2.63)and(21.39±5.23)mmol/L respectively,and those of CaSki cells were(9.98±1.63)and(7.47±2.09)mmol/L,resepectively.The content of G_(2)/M phase cells decreased and S phase cells increased in Met group(P<0.05).The apoptosis rate of Met group was higher than that of control group(P<0.05).The expression of p-AMPK in the Met group was higher than that in the control group,while p-S6K and p-4E-BP1 were lower(P<0.05).Conclusions The inhibitory effect of metformin on the proliferation of cervical squamous cell carcinoma lines may be related to the mechanism of promoting apoptosis,blocking cell cycle at S phase and activation of AMPK-mTOR signal pathway.

关 键 词：二甲双胍 宫颈鳞癌细胞系 细胞周期 细胞凋亡 哺乳动物雷帕霉素靶蛋白 

分 类 号：R711.7[医药卫生—妇产科学]