Sorafenib blocks the HIF-1α/VEGFA pathway, inhibits tumor invasion, and induces apoptosis in hepatoma cells

Ming Xu, Yan-ling Zheng, Xiao-yan Xie, Jin-yu Liang, Fu-shun Pan, Shu-guang Zheng, Ming-de Lü
DNA and Cell Biology 2014, 33 (5): 275-81
Hypoxia and hypoxia-driven angiogenesis play an important role on the recurrence of hepatocellular carcinoma after insufficient radiofrequency ablation. The hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor-A (VEGFA) pathway plays an important part in this process. Sorafenib is a multikinase inhibitor with activity against several receptor tyrosine kinases. However, it is unclear whether sorafenib can affect the HIF-1α/VEGFA pathway. Here, we explore whether sorafenib affects HIF-1α and the change of invasion ability in this process. In this experiment, the control group, cobalt chloride (CoCl2)-treated group, sorafenib-treated group, and cobalt chloride combined with sorafenib-treated group were adopted. Western blot and PCR were performed to detect the protein and mRNA expression of HIF-1α and VEGFA in different groups. Transwell assay was used to test the changes of invasion ability. Flow cytometry was adopted to detect the apoptotic role of sorafenib on hepatoma cells. Cobalt chloride upregulated the expression of HIF-1α protein, and the upregulation effect was more obvious when the concentration was increased gradually. Sorafenib inhibited cobalt-induced HIF-1α and VEGFA expression in hepatoma cells. Sorafenib decreased the tumor cell invasiveness induced by cobalt chloride in vitro. Sorafenib inhibited cell proliferation and induced apoptosis in hepatoma cells. These results showed that sorafenib was an effective inhibitor of the HIF-1α/VEGFA pathway, which can provide new insight into the mechanism of its anticancer activity.

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