In vitro metformin anti-neoplastic activity in epithelial ovarian cancer
In vitro metformin anti-neoplastic activity in epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2008.04.008
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Bruchim, Ilan
中科院分区：
文献类型：
--
作者：
Gotlieb, Walter H.;Saumet, Julio;Bruchim, Ilan
Objective.二甲双胍是治疗II型糖尿病的常用药物，可降低癌症风险并改善癌症预后。我们评估了其对上皮性卵巢癌细胞系的作用。将OVCAR-3和OVCAR-4细胞系暴露于二甲双胍（含和不含顺铂）。使用Alcohol比色测定法进行细胞毒性测定，一式三份。二甲双胍暴露后，通过Western印迹法检测总AMPK、磷酸化AMPK、p70 S6 K和S6 K的水平。二甲双胍诱导OVCAR-3和OVCAR-4细胞系的剂量和时间依赖性生长抑制。二甲双胍在体外增强顺铂的作用。AMPK抑制剂化合物C可部分消除代谢产物的生长抑制作用。Western blotting结果显示，二甲双胍在细胞毒性浓度下可诱导AMPK磷酸化，降低p70 S6 K和S6 K磷酸化，提示其抗增殖作用的机制。二甲双胍显著抑制卵巢癌细胞系的生长并增强顺铂。正在进行进一步的临床前研究，以确定二甲双胍在卵巢癌治疗中的适用性。(c)2008年爱思唯尔公司All rights reserved.
Objective. Metformin, a commonly used drug in the treatment of type II diabetes, may reduce cancer risk and improve cancer prognosis. We evaluated its effect on epithelial ovarian cancer cell lines.Methods. The OVCAR-3 and OVCAR-4 cell lines were exposed to metformin with and without cisplatin. Cytotoxicity assays were performed in triplicates using the Alamar colorimetric assay. Levels of total and phosphorylated AMPK, p70S6K and S6K were evaluated by Western blotting following exposure to metformin.Results. Metformin induces dose- and time-dependent growth inhibition of OVCAR-3 and OVCAR-4 cell lines. Metformin potentiated the effect of cisplatin in vitro. Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.Conclusion. Metformin significantly inhibits the growth of ovarian cancer cell lines and potentiates cisplatin. Further pre-clinical studies are being conducted to determine the applicability of metformin in the treatment of ovarian cancer. (c) 2008 Elsevier Inc. All rights reserved.