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A KB cell line resistant to cisplatin (KB-rc cell) was successfully established by exposing KB cells to a gradually increasing dose of cisplatin in vitro. The concentration of cisplatin required for 50% inhibition of KB-rc cell proliferation was 1.0 micrograms/ml, while that of KB cells was 0.5 micrograms/ml. Studies of KB-rc cell kinetics after treatment with cisplatin, using flow cytometry, showed that the G2M phase block was inhibited on day 3, and that G0G1 phase cells started to increase on day 5. Therefore, cisplatin-resistance is related to inhibition of the G2M phase block. The decrease of KB-rc cell viability with cisplatin was accelerated by the addition of a Ca antagonist (verapamil) and S phase cells increased on day 3. Verapamil may therefore be useful for enhancement of the effect generated by cisplatin on cisplatin-resistant tumor cells.
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