Antitumor effect of metformin in esophageal cancer: In vitro study
Antitumor effect of metformin in esophageal cancer: In vitro study
复制标题
DOI：
10.3892/ijo.2012.1722
复制
发表时间：
2013-02-01
影响因子：
5.2
通讯作者：
Masaki, Tsutomu
中科院分区：
文献类型：
--
作者：
Kobayashi, Mitsuyoshi;Kato, Kiyohito;Masaki, Tsutomu
最近的研究表明，二甲双胍是双胍家族的一员，通常被用作口服降糖药，可以降低癌症风险并改善多种癌症的预后。然而，二甲双胍对食管癌的抗肿瘤作用机制尚不清楚。本研究的目的是评估二甲双胍对体外人ESCC增殖的影响，并研究microrna （mirna）表达谱的变化，因为mirna之前与二甲双胍在其他人类癌症中的抗肿瘤作用有关。以体外培养的人ESCC细胞系T.T、KYSE30和KYSE70为实验材料，研究二甲双胍对人ESCC的影响。此外，我们使用miRNA阵列提示来探索在二甲双胍治疗和不治疗的KYSE30细胞中miRNA之间的差异。二甲双胍对体外培养的t细胞、KYSE30细胞和KYSE70细胞的增殖有抑制作用。二甲双胍阻断体外G0/G1细胞周期。这种阻断伴随着G1细胞周期蛋白，尤其是细胞周期蛋白D1，以及细胞周期蛋白依赖性激酶（Cdk）4、Cdk6和磷酸化视网膜母细胞瘤蛋白（Rb）的减少。此外，体外二甲双胍处理显著改变了mirna的表达。二甲双胍抑制了三种ESCC细胞系的生长，这种抑制可能与细胞周期蛋白D1、Cdk4和Cdk6的减少有关。
Recent studies suggest that metformin, which is a member of the biguanide family and commonly used as an oral anti-hyperglycemic agent, may reduce cancer risk and improve prognosis of numerous types of cancer. However, the mechanisms underlying the antitumor effect of metformin on esophageal cancer remain unknown. The goal of the present study was to evaluate the effects of metformin on the proliferation of human ESCC in vitro, and to study changes in the expression profile of microRNAs (miRNAs), since miRNAs have previously been associated with the antitumor effects of metformin in other human cancers. The human ESCC cell lines T.T, KYSE30 and KYSE70 were used to study the effects of metformin on human ESCC in vitro. In addition, we used miRNA array tips to explore the differences between miRNAs in KYSE30 cells with and without metformin treatment. Metformin inhibited the proliferation of T.T, KYSE30 and KYSE70 cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, as well as decreases in cyclin-dependent kinase (Cdk)4, Cdk6 and phosphorylated retinoblastoma protein (Rb). In addition, the expression of miRNAs was markedly altered with the treatment of metformin in vitro. Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6.