Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

<正> Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion andmetastasis.However,the regulation mechanism remains unknown.Recent studies have shown that several cytokinescan regulate the expression of vascular endothelial growth factor in tumor cells.In this study,we investigated whetherhepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR.Western blot assaywas performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathwaysin colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased incolorectal carcinoma subjects.In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levelsof vascular endothelial growth factor in colorectal carcinoma cells.Hepatocyte growth factor induced phosphorylation ofc-Met,ERK1/2 and AKT in a dose-dependent manner.Specific inhibitors on MEK and PI3K inhibited the hepatocytegrowth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascularendothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.