Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage of combined effects of TNP-470 and SN-38.
The combined effects of TNP-470, a promising antiangiogenic agent, and SN-38, a camptothecin derivative, were evaluated in four human cultured cell lines derived from non-small cell lung cancer (NSCLC). Cytotoxicity experiments were determined by using a tetrazolium salt (MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentrations on these cell lines were 47.3-139.8 microM. Evaluation of drug interactions with isobologram and the combination index values showed that sequential exposure to SN-38 followed by TNP-470 produced synergistic effects in the four cell lines tested. Our findings suggest that such an angiocytotoxic chemotherapy might be promising for the treatment of NSCLC.
Satoh
H
H
Department of Respiratory Medicine, Institute of Clinical Medicine, and University of Tsukuba, Tsukuba-city, Japan. hirosato@md.tsukuba.ac.jp
Ishikawa
H
H
Fujimoto
M
M
Fujiwara
M
M
Yamashita
Y T
YT
Yazawa
T
T
Ohtsuka
M
M
Hasegawa
S
S
Kamma
H
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D003510:Cyclohexanes; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077146:Irinotecan; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D002166:Camptothecin