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二甲双胍抑制大鼠嗜铬细胞瘤细胞的增殖和活力。

Metformin Suppresses Proliferation and Viability of Rat Pheochromocytoma Cells.

作者信息

Li Min, Jiang Xiuli, Su Tingwei, Jiang Lei, Zhou Weiwei, Wang Weiqing

机构信息

Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China (mainland).

出版信息

Med Sci Monit. 2017 Jul 4;23:3253-3260. doi: 10.12659/msm.903348.

Abstract

BACKGROUND Previous studies have clearly demonstrated that metformin inhibits cell proliferation and cell growth in many types of human cancers. Increased survival rates in patients with breast and lung cancer receiving metformin have also been observed. However, the effect of metformin on pheochromocytoma cells remains unexplored. MATERIAL AND METHODS Rat pheochromocytoma cells (PC12 cells) were cultured and treated with metformin or vehicle control. Cell proliferation, cell-cycle, apoptosis, genes expression, and the signaling pathways involved were analyzed in PC12 cells. RESULTS The metformin treatment reduced cell viability and proliferation in rat pheochromocytoma PC12 cells in a dose- and time-dependent manner. Furthermore, metformin exposure led to an increased apoptosis rate and cell-cycle arrest accompanied with downregulation of Ccna2 and Ccnb2. At the molecular level, the AMPK signaling pathway was activated, whereas the mTOR and ERK1/2 signaling pathways were inhibited by metformin. CONCLUSIONS Our data suggest an antiproliferative role of metformin in pheochromocytoma development, which may provide a novel option for future cancer therapy.

摘要

背景 先前的研究已清楚表明,二甲双胍可抑制多种人类癌症中的细胞增殖和细胞生长。接受二甲双胍治疗的乳腺癌和肺癌患者的生存率也有所提高。然而,二甲双胍对嗜铬细胞瘤细胞的作用仍未得到探索。

材料与方法 培养大鼠嗜铬细胞瘤细胞(PC12细胞),并用二甲双胍或溶剂对照进行处理。对PC12细胞的细胞增殖、细胞周期、凋亡、基因表达及相关信号通路进行分析。

结果 二甲双胍处理以剂量和时间依赖性方式降低了大鼠嗜铬细胞瘤PC12细胞的活力和增殖。此外,二甲双胍处理导致凋亡率增加和细胞周期停滞,并伴有Ccna2和Ccnb2的下调。在分子水平上,AMPK信号通路被激活,而mTOR和ERK1/2信号通路被二甲双胍抑制。

结论 我们的数据表明二甲双胍在嗜铬细胞瘤发生中具有抗增殖作用,这可能为未来的癌症治疗提供一种新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4057/5507802/42ed0d36f30f/medscimonit-23-3253-g001.jpg

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