Synergism of cisplatin and mitomycin C in sensitive and resistant cell subpopulations of a tumor model

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Abstract
Cisplatin is a widely-used anti-neoplastic agent with activity against a broad spectrum of human solid tumors. It is, however, seldom curative as a single agent. In an in vitro tumor model system, V79 spheroids, the non-cycling, hypoxic cell subpopulations are most resistant to cisplatin, suggesting that combination chemotherapy with cisplatin and a drug which preferentially killed hypoxic cells might prove useful. Mitomycin C has the latter activity, and was thus evaluated. Not only was the expected complementary toxicity observed in combination treatments, but synergism between the drugs was found at clinically relevant drug doses. Further, both the net pattern of cell killing and the degree of interaction between the agents were a function of the dose ratios of the drugs in the combination treatments. The ability of mitomycin C to potentiate the response of cells resistant to cisplatin as a single agent may thus prove of value in clinical protocols.