分裂原激活蛋白激酶p38信号传导通路在抑制血管内皮细胞生长因子诱导肝癌转移的实验研究

The effect of signal passway of mitogen-activated protein kinase on hepatocellular carcinoma metastasis induced by VEGF

目的 研究血管内皮细胞生长因子 (vascularendothelialgrowthfactor ,VEGF)诱导肝癌转移时 p38分裂原激活蛋白激酶 (mitogen activatedproteinkinase,MAPK)信号传导通路的作用。 方法 运用Bodyenchamber膜侵袭培养系统 ,应用 p38MAPK信号传导通路特异性阻断剂SB 2 0 35 80 ,观察其对VEGF诱导肝癌细胞转移抑制作用。结果 5ng/mlVEGF培养 5h ,向下室浸润肝癌细胞数为 16×10 4 /ml,高于对照组 1.2 5× 10 4 /ml,P <0 .0 1。预先用 5 μMSB 2 0 35 80 ,可阻断 95 %VEGF诱导肝癌转移能力。结论 VEGF通过 p38MAPK信号传导通路诱导肝癌细胞转移 ,阻断p38MAPK信号传导通路 ,可抑制VEGF诱导的肝癌细胞转移。

Objective To study the effect of signal transduction blockage p38 mitogen activated protein kinase(MAPK) for metastasis of hepatocellular carcinoma induced by vascular endothelial growth factor (VEGF). Methods By membrane invasion culture system (mics), we used the SB 203580, an inhibitor of p38 MAPK to observe it's effect on blocking metastasis of hepatocellular carcinoma induced by VEGF. Result The cells in lower compartment with or without SB 203580 were 16×10 4/ml and 0.75×10 4/ml, respectively, after cultured for 5 hours with 5ng/ml VEGF, which was remarkably higher than 1.25×10 4/ml in control group, P <0.01. Conclusions VEGF can induce metastasis of hepatocellular carcinoma but can be blocked by SB 203580 which is an inhibitor of p38 MAPK. VEGF induces metastasis of hepatocellular carcinoma by p38 MAPK signal transduction.