HM-3-HSA exhibits potent anti-angiogenesis and antitumor activity in hepatocellular carcinoma

HM-3-HSA is an antitumor fusion protein which improved the pharmacokinetics of HM-3. Previous studies reported that HM-3-HSA enhanced antitumor activity of HM-3 in melanoma cells. However, the efficacy and the mechanism of HM-3-HSA in hepatocellular carcinoma, especially its effect on tumor angiogenesis, have not been elucidated. Herein, we showed that HM-3-HSA significantly inhibited the H22 and SMMC-7721 tumor xenografts growth and tumor angiogenesis in vivo, indicating the antitumor activity exerted by HM-3-HSA was closely corrected with its potency on tumor angiogenesis. To investigate the anti-angiogenic mechanism, we evaluated the efficacy of HM-3-HSA in HUVECs in vitro. The results showed that multiple steps of tumor angiogenesis, including endothelial cell proliferation, migration, invasion and tube formation, were substantially inhibited by HM-3-HSA. Mechanism investigations revealed that HM-3-HSA could bind HUVECs via integrin αvβ3 and α5β1 and inhibited phosphorylation of the downstream protein kinases including FAK, Src and PI3 K. Our study was the first to report the activity of HM-3-HSA against hepatocellular carcinoma and tumor angiogenesis as well as the underlying mechanism by which HM-3-HSA to exert its anti-angiogenic activity.