Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo
Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo
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DOI：
10.1016/j.mce.2014.05.021
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发表时间：
2014-08-05
影响因子：
4.1
通讯作者：
Park, Do Joon
中科院分区：
文献类型：
--
作者：
Cho, Sun Wook;Yi, Ka Hee;Park, Do Joon
二甲双胍是一种用于治疗2型糖尿病的抗糖尿病药物，据报道在几种人类癌症中具有预防或治疗作用。本研究探讨了治疗性。二甲双胍在PTC中的生理剂量电位。不同剂量（0.5 ~ 20 mM）的二甲双胍抑制BCPAP和BHP10-3SC细胞的PTC细胞活力，增加细胞凋亡。Western blot分析显示，p-AMPK/AMPK比值随着二甲双胍处理的增加而增加。采用BHP10-3SC细胞和胸腺裸鼠进行异位瘤实验。在肿瘤发展模型和已建立的肿瘤模型中，口服饮水二甲双胍均可显著延缓肿瘤的生长。二甲双胍治疗后肿瘤坏死面积明显增加。Western blot分析显示，与模拟对照组相比，二甲双胍处理小鼠的p-AMPK/AMPK比值升高，mTOR和Akt表达抑制。我们的研究结果表明，生理剂量的二甲双胍通过激活AMPK信号和抑制Akt信号而具有抗肿瘤作用。2014爱思唯尔爱尔兰有限公司版权所有。
Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported to have oncopreventive or therapeutic roles in several human cancers. The present study investigated the therapeutic. potential of physiologic dose of metformin in PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in various doses (0.5-20 mM) in BCPAP and BHP10-3SC cells. Western blot analysis demonstrated that the p-AMPK/AMPK ratio increased with increased metformin treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and athymic nude mice. Oral metformin treatment via drinking water significantly delayed tumor growth in both tumor development model and established tumor models. Necrotic area in tumors significantly increased with metformin treatment. Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice. Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and Inhibition of Akt signaling. (C) 2014 Elsevier Ireland Ltd. All rights reserved.