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

Objective: hepatocellular carcinoma (hcc), one of the most common cancers worldwide,is resistant to anticancer drugs. angiogenesis is a major cause of tumor resistance tochemotherapy, 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 rnatargeting vegf gene (vegf-sirna) on chemosensitivity of hcc cells in vitro.materials and methods: in this experimental study, transfection was performed on hep3bcells. after transfection with sirnas, vegf mrna and protein levels were examined. cellproliferation, apoptosis and anti-apoptotic gene expression were also analyzed after treatmentwith vegf-sirna in combination with doxorubicin in hep3b cells.results: transfection of vegf-sirna into hep3b cells significantly reduced the expressionof vegf at both mrna and protein levels. combination therapy with vegf-sirnaand doxorubicin more effectively suppressed cell proliferation and induced apoptosis thanthe respective monotherapies. this could be explained by the significant downregulationof b-cell lymphoma 2 (bcl-2) and survivin.conclusion: vegf-sirna enhanced the chemosensitivity of doxorubicin in hep3bcells at least in part by suppressing the expression of anti-apoptotic genes. therefore,the downregulation of vegf by sirna combined with doxorubicin treatment hasbeen shown to yield promising results for eradicating hcc cells.