STUDIES ON ANTITUMOR ACTIVITY OF rhENDOSTATIN

AIMTo investigate the inhibitory effect of recombinant human endostatin (rhEndostatin) on endothelia cell proliferation and tumor growth. METHODSMTT assay was applied to examine the anti-proliferation of rhEndostatin on human embryo umbilical cord vascular endothelial cell ECV304 and human cancer cell HCT-8, BGC803 and EJ. Xenotransplanted nude mice models with human cancer and experimental implanted tumor mice model were used to evaluate rhEndostatin's antitumor activity. RESULTSrhEndostatin was shown to inhibit the proliferation of ECV304 cells and the IC₅₀ is about 7×10-6 g·L^-1. No inhibition was observed in HCT-8, BGC803 and EJ cells at 1×10^-4 g·L^-1 rhEndostatin. rhEndostatin was shown to inhibit human xenograft in nude mice with human gastric cancer BGC803 and breast cancer B37 when administered subcutaneously at 5, 10, 20 mg·kg^-1·d^-1 for 24 days in a dose-dependent manner. Mouse hepatoma H22 was also suppressed when given rhEndostatin subcutaneously 20 mg·kg^-1·d^-1 for 9 days, but it showed no inhibitory effect on Lewis lung carcinoma and B16 melanoma. CONCLUSIONThese results indicate that rhEndostatin can inhibit the growth of xenotransplanted human tumors in nude mice and certain murine tumor. The action mechanism may be that it can inhibit endothelial cell proliferation, thereby inhibiting the formation of new blood vessel in tumor, leading the tumor to stop grow.