肝癌细胞VEGF转录调控的信号传导通路

Signal transduction pathways in regulation of transcription of vascular endothelial growth factor in hepatocellular carcinoma cells

目的 研究磷脂酰肌醇3 激酶(PI3K)和p42/p44丝裂源激活的蛋白激酶(MAPK)在 肝癌细胞血管内皮生长因子(VEGF)转录调控中的作用。方法 应用缺氧诱导剂氯化钴或重组人表 皮生长因子(EGF)刺激HepG2细胞中VEGF的转录,在此过程中应用PI3K特异性阻断剂 LY294002或p42/p44MAPK特异性阻断剂PD98059干预,采用半定量逆转录PCR检测VEGF mRNA表达的变化。结果 氯化钴或EGF可以诱导HepG2细胞中VEGF的表达。PI3K阻断剂 LY294002可以在一定范围内浓度依赖性地抑制VEGFmRNA的表达,而p42/p44MAPK阻断剂 PD98059对VEGFmRNA的表达无抑制作用。结论 肝癌细胞VEGF的转录调控受PI3K通路调 控,而不受p42/p44MAPK调控。

Objective To investigate the roles of phosphatidylinositol 3-kinase (PI3K) and p42/p44 MAPK in the regulation of transcription of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) cells. Methods The transcription of VEGF was stimulated by hypoxia-inducer cobalt chloride or recombinant human epidermal growth factor (EGF). During the course, specific inhibitor of PI3K (LY294002) and p42/p44 MAPK (PD98059) was used. VEGF mRNA was detected through semiquantitative reverse transcriptional polymerase chain reaction. Results Cobalt chloride or EGF could induce the expression of VEGF induced by cobalt chloride or EGF, but even 20 (M LY294002 could not completely block the expression of VEGF. PD98059 had no inhibitory effects on the transcription of VEGF. Conclusions The transcription of VEGF in HCC cells is regulated by PI3K but not p42/p44 MAPK.