Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice.
OBJECTIVE
To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism.


METHODS
Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups. Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested, the tumor volumes were determined, and the expressions of CD34, VEGF and Flk-1 were examined by immunohistochemical method.


RESULTS
Tumor volume was significantly inhibited in the endostatin group (84.17%) and tumor weight was significantly inhibited in the endostatin group (0.197+/-0.049) compared to the control group (1.198+/-0.105) (F = 22.56, P = 0.001), microvessel density (MVD) was significantly decreased in the treated group (31.857+/-3.515) compared to the control group (100.143+/-4.290) (F = 151.62, P<0.001). Furthermore, the expression of Flk-1 was significantly inhibited in the treated group (34.29%) compared to the control group (8.57%) (chi(2) = 13.745, P = 0.001). However no significant decrease was observed in the expression of vascular endothelial growth factor (VEGF) between these two groups (chi(2) = 0.119,P = 0.730).


CONCLUSIONS
Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/Flk-1 pathway. This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.
Jia
Yun-He
YH
Department of Abdominal Surgery, Tumor Hospital of Harbin Medical University, Heilongjiang Province, China. jyhcruse@0451.com
Dong
Xin-Shu
XS
Wang
Xi-Shan
XS
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D043169:Endostatins / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2