SU11274抑制人子宫内膜癌细胞增殖的分子机制

目的:探索HGF/c-met传导通路抑制剂SU11274抑制子宫内膜癌细胞增殖的分子机制。方法:使用不同浓度SU11274(0.5μmol/L、1.0μmol/L、1.5μmol/L)作用ishikawa和HEC-1B两种细胞株1小时后,加入40 ng/ml的HGF,继续培养48小时,然后使用RT-PCR检测c-met、Survivin、XIAP水平以及Western blot检测细胞中Survivin、XIAP蛋白表达水平。结果:ishikawa细胞c-met低表达,而HEC-1B细胞c-met明显高表达,HEC-1B细胞中c-met mRNA表达量为ishikawa中的2.5倍。SU11274可以使HEC-1B、ishikawa细胞的Survivin、XIAP蛋白表达下调,呈现剂量依赖性,并且在HEC-1B细胞中,该下调作用明显强于ishikawa细胞(P<0.05)。结论:SU11274可以通过下调HGF/c-met传导通路中Survivin、XIAP的表达来抑制人子宫内膜癌细胞增殖。

Study on the molecular mechanism of SU11274 inhibiting the proliferation of human endometrial carcinoma cells

Objective:To explore the molecular mechanism of SU11274，an inhibitor of HGF/c-met pathway，in inhibiting the proliferation of endometrial cancer cells.Methods:Two different cell lines，ishikawa and HEC-1B，were treated with different concentrations of SU11274 (0.5 μmol/L，1.0 μmol/L，1.5 μmol/L) for 1 hour.40 ng/ml of HGF was added，and culture was continued for 48 hours.The levels of c-met，Survivin and XIAP were detected by RT-PCR and the expression of Survivin and XIAP in the cells was detected by Western blot.Results:The expression of c-met was lower in ishikawa cells，while the expression of c-met was significantly higher in HEC-1B cells.The expression of c-met mRNA in HEC-1B cells was 2.5-fold higher than that in ishikawa.SU11274 can down-regulate the expression of Survivin and XIAP proteins in HEC-1B and ishikawa cells in a dose-dependent manner，and the down-regulation of HEC-1B cells was significantly stronger than that of ishikawa cells (P<0.05).Conclusion:SU11274 can inhibit the proliferation of human endometrial cancer cells by down-regulating the expression of Survivin and XIAP in HGF/c-met pathway.