金雀异黄素对胃癌细胞增殖的影响及对microRNA-27a和FOXO1的调控

目的 探讨人微小RNA-27a(microRNA-27a,miR-27a)及其靶基因FOXO1在胃癌组织、癌旁组织中的变化及其在金雀异黄素抑制胃癌细胞增殖中的作用.方法 利用Real Time PCR方法检测10对胃癌癌旁/癌组织中microRNA-27a及其靶基因FOXO1 mRNA的表达.不同浓度(5、10、20、40 μmol·L-1)的金雀异黄素作用于胃癌细胞SGC 7901 72 h后,用噻唑兰比色法(MTT)检测细胞增殖,并采用Real Time PCR方法检测细胞中miR-27a及其靶基因FOXO1 mRNA的表达.结果 胃癌组织较癌旁组织miR-27a表达升高(1.566±0.206 5),其靶基因FOXO1 mRNA表达降低(0.298±0.156 6).Pearson线性分析表明:miR-27a与FOXO1 mRNA呈负相关(r=-0.701 8).金雀异黄素作用于SGC-7901细胞后,细胞增殖得到了抑制,尤其在20与40μmol·L-1浓度下,细胞抑制率明显降低.不同浓度的金雀异黄素处理72 h后,miR-27a表达与对照组比较明显降低；其靶基因FOXO1mRNA表达水平较对照组增加(均P＜0.05).结论 金雀异黄素可能通过抑制miR-27a表达,促进FOXO1 mR-NA的表达,进而抑制胃癌细胞增殖,发挥抗肿瘤的作用.

Effect of genistein on gastric cell proliferation and regulation on miR-27a and FOXO1

Objective To investigate the effect of genistein on microRNA-27a(miR-27a) as well as on its target gene FOXO1 expression levels.Methods Relative expression levels of miR-27a and FOXO1 in 10 paired normal gastric samples and gastric carcinoma samples were detected by real-time PCR.After treating SGC-7901 cells with different concentrations of genistein for 72 h,cell proliferation was determined by MTT assay,and the relative expression changes of miR-27a and FOXO1 were measured by real-time PCR.Results MiR-27a was up-regulated in gastric carcinoma samples compared with normal gastric samples.Meanwhile,FOXO1 was down-regulated in gastric carcinoma.Pearson assay showed an inverse correlation between miR-27a and FOXO1 mRNA(r=-0.701 8).Genistein significantly inhibited the cell proliferation in a dose-dependent manner.Further functional assays revealed that the levels of miR-27a and its target gene FOXO1 were significantly different based on the dose of genistein.Conclusion Genistein inhibits the expression of miR-27a and increases the expression of FOXO1 mRNA in human gastric cells.