Antiangiogenic and antitumor effects of tranilast on mouse lung carcinoma cells.
We examined the effects of tranilast on tumor angiogenesis, tumor growth and metastasis in the mouse Lewis lung carcinoma and C57BL mouse system. Tranilast significantly reduced the dense capillary network induced by Lewis lung cancer cells in a mouse dorsal air sac angiogenesis model. Intraperitoneal administration of tranilast at 200 mg/kg/day reduced the tumor size of mouse Lewis lung carcinoma to about 63% of that of the control and suppressed pulmonary metastasis in a spontaneous system. Immunohistochemistry revealed that tranilast reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. Tranilast potentiated the inhibition of the tumor growth induced by cyclophosphamide, cis-diamminedichloroplatinum(II), adriamycin and vindesine in vivo. These results suggest that tranilast has antiangiogenic and antitumor effects and might have possible therapeutic applications.
Yatsunami
J
J
Department of Internal Medicine, Saga Medical School, Saga 849-8501, Japan. yatsunam@post.saga-med.ac.jp
Aoki
S
S
Fukuno
Y
Y
Kikuchi
Y
Y
Kawashima
M
M
Hayashi
S I
SI
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D003510:Cyclohexanes; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014751:Vindesine / Q000494:pharmacology / Q000627:therapeutic use; D062367:ortho-Aminobenzoates / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D012717:Sesquiterpenes; D062367:ortho-Aminobenzoates; D004317:Doxorubicin; D003520:Cyclophosphamide; C012293:tranilast; D002945:Cisplatin; D014751:Vindesine; D000077609:O-(Chloroacetylcarbamoyl)fumagillol