T. Sunami, K. Nishio, F. Kanzawa
1999
Citations
1
Influential Citations
20
Citations
Quality indicators
Journal
Cancer Chemotherapy and Pharmacology
Abstract
Purpose: TAS-103 [6-((2-(dimethylamino) ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride] is a newly synthesized dual inhibitor of topoisomerase I and II. Since anticancer drugs are used in combination with other drugs for effective chemotherapy, we investigated the cytotoxic effect of TAS-103 in combination with other conventional anticancer agents, such as cisplatin, vindesine, doxorubicin, 5-fluorouracil, and the antitopoisomerase inhibitors SN-38 and etoposide in vitro. Methods: Inhibition of the growth of the human small-cell lung cancer cell line SBC-3 was evaluated using the tetrazolium dye (MTT) assay. Drug interactions were evaluated by isobologram analysis and the determination of combination indices supplemented by a three-dimensional model. Results: Simultaneous use of TAS-103 and cisplatin had a supradditive effect, but combinations of TAS-103 with other drugs had an additive or marginally subadditive effect. Three-dimensional model analysis added more information about the synergistic concentration ranges of two drugs (cisplatin 200–400 nM and TAS-103 7–10 nM). Sequential use of TAS-103 and cisplatin had only an additive effect. Conclusion: These results suggest that the concomitant use of TAS-103 and cisplatin has a greater cytotoxic effect on cancer cells than single drug use, and may provide a beneficial effect in the treatment of small-cell lung cancer.