The anti-angiogenic activity of human endostatin inhibits bladder cancer growth and its mechanism.
OBJECTIVE
We investigated whether recombinant human endostatin can inhibit the growth of bladder cancer in an experimental model and its possible mechanism of action.


METHODS
The recombinant human endostatin protein was induced and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot assays. Its biological activities and the possible mechanisms of action were studied in vitro and in vivo.


RESULTS
Recombinant human endostatin inhibited the proliferation of endothelial cells (ECV304) but not bladder tumor cells (EJ). Endostatin induced the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in bladder cancer cells. Endostatin slowed the growth of xenograft bladder tumors. Immunohistochemistry revealed that endostatin blocked angiogenesis by decreasing vascular endothelial growth factor expression and inducing apoptosis in bladder cancer cells.


CONCLUSIONS
These findings demonstrate that endostatin can inhibit xenograft bladder cancer growth and this effect is likely to be mediated by regulating matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and vascular endothelial growth factor expression, and by inducing apoptosis.
Du
Zhijun
Z
Department of Urology, Peking University People's Hospital, Peking, People's Republic of China.
Hou
Shukun
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D043169:Endostatins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043169:Endostatins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2