雄激素和雄激素受体对肝癌细胞株PEG10表达的作用

目的 探讨雄激素和雄激素受体(AR)对肝癌细胞株PEG10表达的调控作用.方法 设计合成针对人ARsiRNA,并转染HepG2和7404肝癌细胞株.用双氢睾丸酮(DHT)干预HepG2细胞.Western Blot检测AR和PEG10表达水平.结果 从3对AR siRNA中筛选到1对siRNA(AR siRNA-3),它在2种肝癌细胞株中均可有效抑制AR的表达,其抑制作用呈剂量依赖关系.2种肝癌细胞株中,浓度为240 nmol/L的AR siRNA-3在转染后24 h,对AR抑制效率可达80%以上,且抑制效果可持续至72 h.AR siRNA-3转染24h后PEG10表达水平降低,转染48 h后,PEG10表达水平降低非常明显,72 h后PEG10表达有所上升.DHT可促进HepG2细胞PEG10的表达,呈剂量依赖关系.DHT对AR表达未见明显作用.结论 雄激素和AR参与了肝癌细胞株PEG10表达的调控.这可能是男性肝细胞癌发病率较高的原因之一.

Effects of androgen and androgen receptor on PEG10 expression in hepatocellular carcinoma cells

Objective To investigate the effects of androgen and androgen receptor (AR) on the expression of PEG10 in hepatocellular carcinoma cells. Methods HepG2 and 7404 cells were treated with androgen (dihydrotestosterone) or synthetic siRNA duplexes targeting human androgen receptor and the level of AR and PEG10 were then examined by Western blot.Results Among 3 siRNA duplexes, one siRNA was picked out which could reduce AR's expression over 84% and 92% at the concentration of 240 nmol/L 24 h post-transfection in HepG2 and 7404 cells respectively. When AR was down-regulated by siRNA, the level of PEG10 was reduced in 24 h and descended to the lowest in 48 h, and increased in 72 h in HepG2 and 7404 cells. The level of PEG10 can be up-regulated by androgen in a dose-dependent manner, but the level of androgen receptor was not affected in HepG2 cells.Conclusion Androgen and AR is involved in the regulation of the PEG10's expression in hepatocellular carcinoma cells, which might be one of the reasons for the higher incidence of hepatocellular carcinoma in the male.