Downregulation of Vascular Endothelial Growth Factor Enhances Chemosensitivity by Induction of Apoptosis in Hepatocellular Carcinoma Cells

Abstract

Objective: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is resistant to anticancer drugs. Angiogenesis is a major cause of tumor resistance to chemotherapy, and vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The purpose of this study is to investigate the impact of small-interfering RNA targeting VEGF gene (VEGF-siRNA) on chemosensitivity of HCC cells in vitro. Materials and Methods: In this experimental study, transfection was performed on Hep3B cells. After transfection with siRNAs, VEGF mRNA and protein levels were examined. Cell proliferation, apoptosis and anti-apoptotic gene expression were also analyzed after treatment with VEGF-siRNA in combination with doxorubicin in Hep3B cells. Results: Transfection of VEGF-siRNA into Hep3B cells significantly reduced the expression of VEGF at both mRNA and protein levels. Combination therapy with VEGF-siRNA and doxorubicin more effectively suppressed cell proliferation and induced apoptosis than the respective monotherapies. This could be explained by the significant downregulation of B-cell lymphoma 2 (BCL-2) and SURVIVIN. Conclusion: VEGF-siRNA enhanced the chemosensitivity of doxorubicin in Hep3B cells at least in part by suppressing the expression of anti-apoptotic genes. Therefore, the downregulation of VEGF by siRNA combined with doxorubicin treatment has been shown to yield promising results for eradicating HCC cells.

Keywords

• Apoptosis
• Doxorubicin
• Hepatocellular Carcinoma Cells
• Small Interfering RNA
• Vascular Endothelial Growth Factor