胆管癌细胞中白细胞介素-6/Stat3通路对c-Met的调控作用

Role of IL-6/Stat3 pathway in the regulation of c-Met in cholangiocarcinoma cells

目的探讨胆管癌细胞中白细胞介素(IL)-6/Stat3和肝细胞生长因子(HGF)/c-Met通路的活化情况及其相互调控作用。方法体外培养胆管癌细胞HCCC-9810,应用Western印迹检测IL-6/Stat3和HGF/c-Met通路的活化及其相互调控,用ELISA试剂盒检测HCCC-9810细胞IL-6和HGF的分泌,RT-PCR检测IL-6/Stat3对c-Met转录的影响。结果胆管癌细胞HCCC-9810中Stat3和c-Met均呈高度磷酸化,HCCC-9810细胞有较高水平IL-6分泌,无HGF分泌。IL-6/Stat3通路通过增强c-Met的稳定性维持胆管癌细胞c-Met的高表达,进而导致c-Met的异常活化。结论胆管癌细胞中IL-6/Stat3信号通路对c-Met的异常活化起重要作用,IL-6/Stat3信号通路能通过c-Met信号通路发挥促胆管癌作用。

Objective To, investigate the activation of the interleukin （IL）-6/signal transducer and activator of transcription 3 （Stat3） and hepatocyte growth factor/c-Met （HGF/c-Met） pathways in human cholangiocarcinoma cells and assess the cross-talk between the IL-6/Stat3 and HGF/c-Met pathways in human cholangiocarcinoma cells. Methods Cholangiocarcinoma cells HCCC-9810 were cultured in vitro. The activation of the IL-6/Stat3 and HGF/c-Met pathways in cholangiocarcinoma cells was measured by Western blot. The cross-talk between the IL-6/Stat3 and HGF/c-Met pathways in cholangiocarcinoma cells was measured by Western blot. The secretion in IL-6 and HGF in cholangiocarcinoma cells was measured by the enzyme-linked immunosorbent assay （ELISA）. The effect of the IL-6/Stat3 pathway on c- Met mRNA levels was assessed by reverse transcription polymerase chain reaction （RT-PCR）. Results HCCC-9810 cells showed strong expression of phosphated Stat3 and phosphated c-Met. The secretion in of IL-6, but not HGF, was detected in HCCC-9810 cells. The IL-6/Stat3 pathway resulted in the abnormal activation of c-Met through enhancing the stability of c-Met. Conclusions In cholangiocarcinoma ceils, the IL-6/Stat3 pathway plays an important role in sustaining the abnormal activation of c-Met. Thus, c-Met is involved in the effect of IL-6/Stat3 on cholangiocarcinoma promotion.