[Studies on antitumor activity of rhEndostatin].
OBJECTIVE
To investigate the inhibitory effect of recombinant human endostatin (rhEndostatin) on endothelia cell proliferation and tumor growth.


METHODS
MTT 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. Xenotrasplanted nude mice models with human cancer and experimental implanted tumor mice model were used to evaluate rhEndostatin's antitumor activity.


RESULTS
rhEndostatin was shown to inhibit the proliferation of ECV304 cells and the IC50 is about 7 x 10(-6) g.L-1. No inhibition was observed in HCT-8, BGC803 and EJ cells at 1 x 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.


CONCLUSIONS
These results indicate that rhEndostatin can inhibit the growth of xenotransplanted human tumors in nude mice and certain murine tumor. The action mechanisms 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.
Li
Hong-yan
HY
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Li
Yan
Y
Liu
Zhong-hai
ZH
Wu
Heng-jia
HJ
Chen
Fei-hu
FH
Chen
Xiao-guang
XG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D043169:Endostatins / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014470:Umbilical Cord / Q000166:cytology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043169:Endostatins; D011994:Recombinant Proteins