ANGIOCYTOTOXIC THERAPY IN HUMAN NONSMALL 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 cultur ed cell lines derived from non-small cell lung cancer (NSCLC). Cytotox icity experiments were determined by using a tetrazolium salt (MTT) as say. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentrations on these cell lines wer e 47.3-139.8 mu M. Evaluation of drug interactions with isobologram an d the combination index values showed that sequential exposure to SN-3 8 followed by TNP-470 produced synergistic effects in the four cell li nes tested. Our findings suggest that such an angiocytotoxic chemother apy might be promising for the treatment of NSCLC.