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

Mol Biol Rep. 2020 Mar;47(3):1883-1893. doi: 10.1007/s11033-020-05282-0. Epub 2020 Feb 3.

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.

Keywords: Combretastatin A-4 disodium phosphate; Hepatocellular carcinoma; Low dose γ-irradiation; ROCK1; VEGF.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / therapy*
  • Chemoradiotherapy
  • Combined Modality Therapy
  • Diethylnitrosamine / adverse effects
  • Down-Regulation
  • Egypt
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic / drug effects
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / therapy*
  • Male
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Rats
  • Rats, Wistar
  • Stilbenes / administration & dosage*
  • Stilbenes / pharmacology
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics*
  • Xenograft Model Antitumor Assays
  • rho-Associated Kinases / genetics*

Substances

  • Antineoplastic Agents, Phytogenic
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Stilbenes
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Diethylnitrosamine
  • ROCK1 protein, rat
  • rho-Associated Kinases
  • fosbretabulin