二甲双胍联合紫杉醇诱导人乳腺癌细胞MCF-7凋亡的作用机制研究

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Abstract Objective To explore the role mechanism of Metformin combined with Paclitaxel in inducing apoptosis of human breast cancer cell MCF-7. Methods CCK-8 kit was used to detect the 50% inhibitory concentration (IC50 value) of cell proliferation after 48 h of single action of different concentrations of Metformin (0.25, 0.50, 1.00, 2.00, 4.00 mmol/L) or Paclitaxel (0.025, 0.050, 0.100, 0.200, 0.400 μmol/L) or two combined action on MCF-7 cell. And the flow cytometry was used to detect the cell cycle distribution after 48 h action of Metformin or Paclitaxel on MCF-7 cell. And Western blot method was used to detect the expression levels of MAPK pathway protein and Bcl-2, Bax proteins after 48 h of single action of Paclitaxel or Metformin or two combined action on MCF-7 cell. Results Low concentration of Metformin (0.25-4.00 mmol/L) combined with Paclitaxel (0.025-0.400 μmol/L) had a synergistic effect (CI<1). sp600125 could significantly inhibite MCF-7 cell proliferation, and the inhibitory effect of MCF-7 cell proliferation by Metformin combined with Paclitaxel was stronger than that by single action of the two. The number of G2/M phase cells by combined action of Metformin and Paclitaxel were less than by single action of Paclitaxel, but more than by single action of Metformin. The expression levels of p-JNK/SAPK and p-p38 proteins after 48 h of Metformin combined with Paclitaxel on MCF-7 cell were significantly higher than those by single action of the two, and the expression levels of p-ERK and Bcl-2 proteins were decreased (P < 0.05). Conclusion Metformin combined with Paclitaxel has a synergistic effect on human breast cancer cell MCF-7, and its inhibitory effect on cells is significantly enhanced when combined with sp600125. Metformin combined with Paclitaxel can inhibit cell aggregation and ERK pathway in G2/M phase, activate JNK and p38 pathway, and reduce the ratio of Bcl-2 and Bax proteins.

Key words： Metformin Paclitaxel Breast cancer MCF-7 cell MAPK pathway

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	LIANG Junwei1 FANG Zhihua2 LI Qingshan1 LYU Xiying1

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LIANG Junwei1 FANG Zhihua2 LI Qingshan1 LYU Xiying1. Role mechanism of Metformin combined with Paclitaxel in inducing apoptosis of human breast cancer cell MCF-7[J]. 中国医药导报, 2018, 15(35): 17-21,25.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2018/V15/I35/17

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