Abstract

Hepatocellular carcinoma (HCC) is aprevalent problem worldwide. Chemotherapy, especially cisplatin (CDDP)-basedsystemic chemotherapy, is the best option for advanced liver cancer. However,CDDP resistance is becoming common and hindering the clinical application ofCDDP. Meanwhile, no consensus has been reached regarding the chemotherapeuticuse of vasohibin 2 (VASH2), which promotes the angiogenesis and proliferationof cancer cells. In this work, a tissue microarray was used to observe VASH2and its possible role in cancer treatment. Results showed that VASH2 was highlyexpressed in HCC tissues and was significantly correlated with cancerdifferentiation. To further investigate the efficacy and mechanism of thecombination of VASH2 with anti-cancer drugs in liver cancer cells, we stablybuilt VASH2 overexpression and knockdown cell lines. We found that VASH2 caninfluence the CDDP sensitivity and that the cell overexpression of VASH2 had ahigher cell viability and lower apoptosis rate after CDDP exposure. We alsoobserved that VASH2 overexpression downregulated wild-type p53, as well assuppressed the expression of the pro-apoptotic protein BCL2-associated Xprotein (Bax) and cleaved caspase-3 (CC-3) after treatment by CDDP. Conversely,the knockdown of VASH2 significantly inhibited these effects. In an in vivochemosensitivity study, nude mice were subcutaneously injected with tumor cellsand received CDDP treatment through intraperitoneal administration every 3days. We found that VASH2 knockdown markedly limited the tumor growth andenhanced the CDDP toxicity and apoptosis of tumor cells. Western blot analysisrevealed that tumor cells with downregulated VASH2 had a higher expression ofwild-type p53, Bax, and CC-3 than control cells. Overall, our results indicatedthe novel roles of VASH2 in the chemoresistance of hepatocarcinoma cells toCDDP and suggested that VASH2 may be a promising anticancer target.