Effect of metformin on apoptosis, cell cycle arrest migration and invasion of A498 cells
Effect of metformin on apoptosis, cell cycle arrest migration and invasion of A498 cells
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二甲双胍对A498细胞凋亡、细胞周期阻滞迁移和侵袭的影响。
DOI：
10.3892/mmr.2014.2097
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发表时间：
2014-06-01
影响因子：
3.4
通讯作者：
Liu, Zhaoxu
中科院分区：
文献类型：
--
作者：
Fang, Zhiqing;Xu, Xiulian;Liu, Zhaoxu
以前的研究表明，二甲双胍（Met）可以降低癌症发生的风险。本实验研究了蛋氨酸对A498细胞的抗肿瘤作用。结果表明，Met可抑制A498细胞增殖，并诱导AMP活化蛋白激酶的激活，呈时间和剂量依赖性。Met可促进A498细胞凋亡，其机制可能是通过下调B细胞淋巴瘤2基因表达，同时上调Bcl-2相关的X蛋白表达而实现的。此外，观察到Met通过降低cyclin D1表达而诱导G1细胞周期阻滞。此外，实验结果表明，Met通过降低基质金属蛋白酶-2抑制A498细胞的迁移和侵袭，表明其具有抑制肾癌转移的潜力。总之，这些结果提供了证据表明，Met在抗肾癌治疗中是重要的，因此可以作为一种新的和有效的药物用于肾癌治疗。
Previous studies have demonstrated that metformin (Met) may reduce the risk of cancer development. In the present study, the anti-cancer effects of Met in A498 cells were investigated. It was found that Met inhibited A498 cell proliferation in a time- and dose-dependent manner, as well as induced the activation of AMP-activated protein kinase. It was also demonstrated that Met promoted A498 cell apoptosis and mechanistic studies suggested that this was mediated by the downregulation of B-cell lymphoma 2 and concurrent upregulation of Bcl-2-associated X protein. In addition, it was observed that Met induced G1 cell cycle arrest by decreasing cyclin D1 expression. Furthermore, the results demonstrated that Met reduced A498 cell migration and invasion in vitro by decreasing matrix metalloproteinase-2, which indicated its potential to inhibit renal cancer metastasis. In combination, these results provide evidence that Met is important in anti-renal cancer therapy, and thus may serve as a novel and efficient agent for renal cancer treatment.