Metformin inhibits renal cell carcinoma in vitro and in vivo xenograft
Metformin inhibits renal cell carcinoma in vitro and in vivo xenograft
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二甲双胍在体外和体内异种移植物中抑制肾细胞癌
DOI：
10.1016/j.urolonc.2011.01.003
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发表时间：
2013-02-01
影响因子：
2.7
通讯作者：
Hu, Weilie
中科院分区：
文献类型：
--
作者：
Liu, Jun;Li, Ming;Hu, Weilie
目的：材料与方法：采用MTT法和集落形成实验研究二甲双胍对肾癌细胞生长的影响。采用流式细胞仪检测二甲双胍处理后细胞周期的变化。我们通过对各种蛋白质的免疫印迹分析进一步确定了参与这一过程的可能的信号分子。此外，异种移植模型被用来研究二甲双胍对RCC肿瘤growth.Results的影响：我们证明，二甲双胍有效地抑制786-O和OS-RC-2 RCC细胞系的细胞增殖。此外，二甲双胍下调细胞周期蛋白D1的表达，并诱导G（0）/G（1）细胞周期停滞在这些细胞。进一步的研究表明，二甲双胍诱导AMP活化蛋白激酶（AMPK）的活化，并抑制哺乳动物雷帕霉素靶蛋白（mTOR），这是蛋白质合成和细胞生长的中心调节因子，并由AMPK负调节。最重要的是，每天用二甲双胍治疗小鼠可以防止异种移植模型中RCC肿瘤的生长。结论：二甲双胍能够诱导G（0）/G（1）细胞周期停滞，并抑制RCC生长在体外和体内。这些结果表明，二甲双胍可能是一种潜在的治疗药物，用于治疗肾细胞癌。(C)2013 Elsevier Inc. All rights reserved.
Objective: To evaluate the effects of metformin on renal cell carcinoma (RCC) and its underlying mechanisms.Materials and methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assays to investigate the effects of metformin on RCC cell growth. Flow cytometry was used to evaluate the cell cycle changes after metformin treatment. We further determined the possible signaling molecules involved in this process by immunoblot analysis of various proteins. Furthermore, a xenograft model was used to study the effects of metformin on RCC tumor growth.Results: We demonstrated that metformin effectively inhibits cell proliferation in 786-O and OS-RC-2 RCC cell lines. Moreover, metformin down-regulated cyclin D1 expression and induced G(0)/G(1) cell cycle arrest in these cells. Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK. Most importantly, daily treatment of mice with metformin prevented RCC tumor growth in a xenograft model.Conclusions: Metformin was able to induce G(0)/G(1) cell cycle arrest and inhibit RCC growth in vitro and in vivo. These results suggest that metformin may be a potential therapeutic agent for the treatment of RCC. (C) 2013 Elsevier Inc. All rights reserved.