Combretastatin A-4 disodium phosphate and low dose gamma irradiation suppress hepatocellular carcinoma by downregulating ROCK1 and VEGF gene expression.

Abstract

Hepatocellular carcinoma (HCC) is a tough opponent. HCC contributes to 14.8% of all cancer mortality in Egypt. There are many choices for management of HCC; however tumor relapse has been reported in animal and clinical studies. This study was conducted to investigate the impact of low dose γ-irradiation (LDR) and combretastatin A-4 disodium phosphate (CA-4DP) on HCC recurrence. HCC was induced in male Wistar albino rats by oral administration of N-nitrosodiethylamine (NDEA) for 17 weeks. We evaluated the expression of the endothelial cell marker (CD31) by immunostaining. Expression of Rho Associated Coiled-Coil Containing Protein Kinase 1(ROCK1) and Vascular endothelial growth factor (VEGF) expression was assessed by real-time PCR after (6, 24 and 48 h). Our results showed that expression of CD31 and gene expression of ROCK1 and VEGF was significantly repressed at all-time intervals by combination therapy ofLDR and CA-4DP as compared with untreated NDEA/HCC group and NDEA/HCC groups treated with either LDR or CA-4DP alone, (P < 0.05). Our study demonstrated the additive effect of LDR in combination with CA-4DP in suppression of HCC.