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

• 研究论文 • 上一篇    下一篇

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*   

  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
  • 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*   

  1. 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: 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

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