Antitumor activities of Liver-targeting peptide modified Recombinant human Endostatin in BALB/c-nu mice with Hepatocellular carcinoma

In our previous study, a liver-targeting peptide CSP I-plus modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed and showed potent antiangiogenic capability and could specifically bind to human hepatocellular carcinoma cells to make a direct inhibition in vitro. In this study, the biological activities of rES-CSP in vivo were evaluated by subcutaneous and orthotopic xenograft nude mice model of human hepatocellular carcinoma cells HepG2. We found that rES-CSP significantly decreased tumor volume to 54.9% in the nude mice with subcutaneous xenograft compared with the control. In orthotopic xenograft model, rES-CSP not only decreased tumor volume (to 39.6% compared with the control) and tumor weight, it also increased its biodistribution in the liver tissue and hepatoma tissue. Moreover, lower microvessel density (MVD) and higher apoptotic index (AI) were also observed in the tumor tissues. It had no significant side-effects on the heart, liver, spleen, lung and kidney of mice. Results indicated CSP I-plus modified Endostar may be a potential candidate for a targeting therapy on hepatocellular carcinoma.