Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage of combined effects of TNP-470 and SN-38

• Published in: Acta oncologica Vol. 37; no. 1; p. 85
• Main Authors: Satoh, H, Ishikawa, H, Fujimoto, M, Fujiwara, M, Yamashita, Y T, Yazawa, T, Ohtsuka, M, Hasegawa, S, Kamma, H
• Format: Journal Article
• Language: English
• Published: England 1998
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Camptothecin - analogs & derivatives; Camptothecin - pharmacology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Division - drug effects; Cyclohexanes; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Irinotecan; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; O-(Chloroacetylcarbamoyl)fumagillol; Sesquiterpenes - pharmacology; Tumor Cells, Cultured - drug effects
• ISSN: 0284-186X
• DOI: 10.1080/028418698423221

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.