Resveratrol inhibits VEGF expression of human hepatocellular carcinoma cells through a NF-kappa B-mediated mechanism.

ABSTRACT

BACKGROUND/AIMS: Resveratrol, a polyphenolic phytochemical present in berries, grapes, and wine, has emerged as a promising chemopreventive candidate. The aim of the present study was to determine the inhibitory effect of resveratrol on vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) and to explore its mechanism. METHODOLOGY: VEGF protein was detected by western blot, whereas VEGF mRNA expression was investigated by RT-PCR. Nuclear factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA). Xenograft sections were stained for CD34 to study microvessels in vivo. RESULTS: We found that VEGF protein and mRNA expressions in the cells treated with resveratrol were significantly decreased. The activation of NF-kappa B was also intensely inhibited by resveratrol. Growth of tumours in nude mice was inhibited by resveratrol. Microvessel density was decreased with resveratrol treatment. CONCLUSIONS: The inhibitory effect of resveratrol on VEGF activity may occur partly through suppression of the activation of NF-kappa B in HepG2 cells. Resveratrol also significantly inhibited tumour growth and angiogenesis.