中国现代医学杂志2018，Vol.28Issue(1)：1-5,5.DOI:10.3969/j.issn.1005-8982.2018.01.001
二甲双胍对人胰腺癌细胞增殖、细胞周期和凋亡的影响及机制
Influence of Metformin on proliferation, cell cycle and apoptosis in human pancreatic adenocarcinoma cells and mechanisms
摘要
Abstract
Objective To investigate the effect of Metformin on proliferation, cell cycle and apoptosis of pancreatic adenocarcinoma Panc-1 cells in vitro, and appraise the possible mechanism. Methods Panc-1 cells were treated with 0.5, 2.0 and 8.0 mmol Metformin in vitro. Cell proliferation was measured by MTT assay. Cell apoptosis and cell cycle distribution were detected by flow cytometery. The expression of PTEN, p-Akt (Ser473)and mTOR were dected by Western blot. Results After 48 h, the inhibition rates of Metformin at dosage of 0.5, 2.0 and 8.0 mmol were (7.20 ± 5.92)％, (18.35 ± 4.77)％ and (33.45 ± 4.10)％, respectively. After 72 h, the inhibition rates of Metformin at dosage of 0.5, 2.0 and 8.0 mmol were (24.81 ± 4.04)％, (53.42 ± 4.18)％ and (61.36 ± 2.00)％, respectively. The proliferation of Panc-1 cells was inhibited by Metformin in a dose- and time-dependent manner. After 48 h, the percentage of G1 phase cells in the 8.0 mmol Metformin group was significantly lower than that in the controlled group and the 0.5 mmol Metformin group (P < 0.05). The percentage of G2/M phase cells in the 8.0 mmol Metformin group was remarkably higher than that in the other groups (P < 0.05). After 48 h, the percentage of cells in the middle and late stages of apoptosis was increased from (7.01 ± 1.14)％ in the controlled group and (6.19 ± 0.32)％ in the 0.5 mmol Metformin group to (12.64 ± 2.74)％ in the 8.0 mmol Metformin group (P < 0.05). After 48 h, compared with the controlled group and the 0.5 mmol Metformin group, the expression of PTEN was activated and the expressions of p-Akt (Ser473) and mTOR were reduced in the 2.0 and 8.0 mmol Metformin groups (P < 0.05). Conclusions Metformin can suppress the proliferation of human pancreatic adenocarcinoma Panc-1 cells, cause G2/M phase checkpoint arrest and induce cell apoptosis in vitro at moderate to high dosage. The mechanism may be inhibition of the PI3K/Akt/mTOR pathway by activating the expression of PTEN.关键词
二甲双胍/胰腺肿瘤/增殖/细胞周期/细胞凋亡/PTEN/PI3K/Akt/mTORKey words
Metformin/pancreatic neoplasm/proliferation/cell cycle/apoptosis/PTEN/PI3K/Akt/mTOR分类
医药卫生引用本文复制引用
徐萍,蒋小猛,葛璐,黄红梅,周朦,张尤历,徐岷..二甲双胍对人胰腺癌细胞增殖、细胞周期和凋亡的影响及机制[J].中国现代医学杂志,2018,28(1):1-5,5.基金项目
国家自然科学基金(No:81472333 （）
No:81672402) （）
