Let-7 g微小RNA使耐氟尿嘧啶的人肝癌细胞致敏。

Let-7 g microRNA sensitizes fluorouracil-resistant human hepatoma cells.

作者信息

Tang Huifang, Zhang Pengfei, Xiang Qiong, Yin Jie, Yu Jia, Yang Xiaoyan, Lei Xiaoyong

出版信息

Pharmazie. 2014 Apr;69(4):287-92.

Abstract

Let-7 microRNA is expressed in lower lever in a variety of human tumors and is involved in tumorigenesis. This study investigated the inhibitory effect of the let-7g microRNA on the expression of the HMGA2 gene in the fluorouracil (5-Fu)-resistant human hepatoma cell line Bel-7402/5-Fu, and the effect of let-7 g microRNA on drug sensitization in Bel-7402/5-Fu cells. Let-7 g microRNA and negative microRNA plasmids were constructed and transient transfected into Bel-7402/5-Fu cells. Expression levels of HMGA2 mRNA and protein in microRNA transient transfectants were clearly reduced as compared with negative microRNA transfectants and untreated cells. Flow cytometry revealed increased in S phase in let-7 g microRNA cells. dimethylthiazol-diphenyltetrazolium bromide (MTT) results indicated that microRNA transfectants had a higher cell inhibition rate than the negative vector or untreated cells after treatment with 0.13-13 microg/ml 5-Fu. In addition, cyclin A was down-regulated in the let-7 g transfectants cells.The results showed that let-7 g microRNA contributed to an increase of 5-Fu-induced cell cycle inhibit in human hepatoma cell and sensitized cells to 5-Fu, leading to increased the effectiveness of the drug in treating hepatoma cancer.

摘要

Let-7微小RNA在多种人类肿瘤中低表达，并参与肿瘤发生。本研究探讨了let-7g微小RNA对氟尿嘧啶（5-Fu）耐药的人肝癌细胞系Bel-7402/5-Fu中HMGA2基因表达的抑制作用，以及let-7g微小RNA对Bel-7402/5-Fu细胞药物敏感性的影响。构建了let-7g微小RNA和阴性微小RNA质粒，并将其瞬时转染到Bel-7402/5-Fu细胞中。与阴性微小RNA转染细胞和未处理细胞相比，微小RNA瞬时转染细胞中HMGA2 mRNA和蛋白的表达水平明显降低。流式细胞术显示let-7g微小RNA细胞的S期增加。噻唑蓝（MTT）结果表明，在用0.13 - 13μg/ml 5-Fu处理后，微小RNA转染细胞比阴性载体或未处理细胞具有更高的细胞抑制率。此外，let-7g转染细胞中细胞周期蛋白A下调。结果表明，let-7g微小RNA有助于增加5-Fu诱导的人肝癌细胞周期抑制，并使细胞对5-Fu敏感，从而提高药物治疗肝癌的有效性。