Sorafenib inhibits growth of hepatoma with hypoxia and hypoxia-driven angiogenesis in nude mice.

Abstract

The study aimed to investigate the effects of sorafenib on growth of hepatoma with hypoxia and angiogenesis. Green fluorescent protein (GFP)-expressing SMMC-7721 hepatoma cells were established via transfection with a lentiviral vector carrying GFP. GFP-labelled cells were treated with CoCl2 for 24 h with or without pretreatment of sorafenib for 30 min, and then injected subcutaneously into nude mice to induce hepatoma xenografts. This study used 16 BALB/c nude mice, which were divided into 4 groups: control group (GFP-labelled cells), CoCl2 group (GFP-labelled cells treated with CoCl2), CoCl2 plus sorafenib group (GFP-labelled cells pretreated with sorafenib and then treated with CoCl2) and CoCl2 plus sorafenib (cell+i.g.) group (GFP-labelled cells pretreated with sorafenib and then treated with CoCl2). After injection, CoCl2 plus sorafenib (cell+i.g.) group received intragastrical administration of sorafenib daily for 40 days. Tumor volume and weight were measured for each mouse. Cy5.5-annexinV and in vivo bioluminescence imaging were used for in vivo detection of cell apoptosis in tumor. Vascular endothelial growth factor (VEGF) and CD 34 were detected by immunohistochemistry. The results showed that, under the hypoxia condition induced by CoCl2, sorafenib pretreatment combined with intragastric administration of sorafenib more obviously suppressed tumor growth and decreased VEGF expression and MVD compared to sorafenib pretreatment alone, and induced cell apoptosis as well. Sorafenib pretreatment combined with intragastric administration is more effective than sorafenib pretreatment alone in the therapy of hepatoma.