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

Document Type : Original Article

Authors

1 Faculty of Biology, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam;Department of Animal Biotechnology, Institute of Tropical Biology, Vietnam Academy of Science and Technology, Ho Chi Minh

2 Department of Animal Biotechnology, Institute of Tropical Biology, Vietnam Academy of Science and Technology, Ho Chi Minh City, Vietnam

3 School of Biotechnology, International University, Vietnam National University, Ho Chi Minh City, Vietnam

4 Faculty of Biology, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

5 4Department of Immunology, Vietnam Military Medical University, Ha Noi City, Vietnam

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