Significant inhibition of endothelial cell growth in tumor vasculature by an angiogenesis inhibitor, TNP-470 (AGM-1470).
Growth inhibition of tumor cells and vascular endothelial cells in M5076 tumors was examined following treatment with TNP-470 to elucidate its antitumor action. The bromodeoxyuridine-labeling index (LI) of tumor and endothelial cells was significantly decreased by TNP-470 treatment to 47 and 9% of the controls, respectively. The LI of endothelial cells was decreased earlier and more extensively than that of tumor cells. In contrast, the LI of endothelial cells was not decreased by treatment with chemotherapeutic agents, adriamycin and cisplatin, at the dose giving a similar growth inhibition on tumor cells. These results suggest that the antitumor action of TNP-470 is exerted by its angiogenesis inhibition.
Yamamoto
T
T
Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan.
Sudo
K
K
Fujita
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003510:Cyclohexanes; D004317:Doxorubicin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012513:Sarcoma, Experimental; D012717:Sesquiterpenes / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D004317:Doxorubicin; D001973:Bromodeoxyuridine; D002945:Cisplatin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol