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

doi:10.16352/j.issn.1001-6325.2023.02.283

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (2): 283-288.doi: 10.16352/j.issn.1001-6325.2023.02.283

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

刘婷婷, 韩超, 赵小玲, 孔为民^*

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

收稿日期:2022-02-17 修回日期:2022-06-29 出版日期:2023-02-05 发布日期:2023-02-02
通讯作者: ^*kwm1967@ccmu.edu.cn
基金资助:
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)

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

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

Received:2022-02-17 Revised:2022-06-29 Online:2023-02-05 Published:2023-02-02
Contact: ^*kwm1967@ccmu.edu.cn

摘要/Abstract

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(IC₅₀)。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 IC₅₀浓度分别为(50.95±2.63)和(21.39±5.23)mmol/L,CaSKi细胞48 和72 h IC₅₀浓度分别为(9.98±1.63)和(7.47±2.09)mmol/L。Met组G₂/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。

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

Abstract: 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 (IC₅₀) 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 IC₅₀ 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 G₂/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.

Key words: metformin, cervical squamous cell carcinoma cell lines, cell cycle, apoptosis, mammalian target of rapamycin

中图分类号:

R711.7

刘婷婷, 韩超, 赵小玲, 孔为民. 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[J]. 基础医学与临床, 2023, 43(2): 283-288.

LIU Tingting, HAN Chao, ZHAO Xiaoling, KONG Weimin. Metformin inhibits proliferation and promotes apoptosis of human cervical squamous cell carcinoma cell lines SiHa and CaSki[J]. Basic & Clinical Medicine, 2023, 43(2): 283-288.

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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

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