Role of signal transduction pathway of mitogen‐activated protein kinase on metastasis of hepatocellular carcinoma induced by VEGF

Abstract

OBJECTIVE: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, infiltration and metastasis in cancer. However, the associated signal transduction pathway remains unclear. The present study aimed to observe the effect of signal transduction induced by VEGF on p38 mitogen-activated protein kinase (MAPK) during metastasis in hepatocellular carcinoma. METHODS: The membrane invasion culture system (MICS) and SB203580, a blocker of p38 MAPK were used to observe the inhibitory effect of VEGF on metastasis in hepatocellular carcinoma. RESULTS: The numbers of cells in the lower compartment of the Boden chamber with or without SB203580 were 16 × 104 and 0.75 × 104/mL, respectively, after being cultured for 5 h with 5 ng/mL VEGF. These values were markedly higher than the number of cells (1.25 × 104/mL) in the control group (P < 0.01). Pretreatment with 5 μmol/L SB203580 was able to block metastatic potential by 95% in hepatic cancer, the hepatocarcinoma cell number cultured for 5 h with 1 ng/mL VEGF, 5 ng/mL VEGF, 10 ng/mL VEGF in amnia was 15, 42 and 28, respectively, as compared with the control (4 cells), these were highly significant (P < 0.05, P < 0.01). When compared with group of 1 ng/mL VEGF, and group 10 ng/mL VEGF, the carcinoma cell number of group of 5 ng/mL VEGF was also highly significant (P < 0.05). CONCLUSIONS: Via the p38 MAPK signal transduction pathway, VEGF is able to induce metastasis in hepatic carcinoma. However, when this particular pathway was blocked with SB203580, then metastasis was inhibited.