SYNERGISTIC ANTITUMOR-ACTIVITY OF MITOMYCIN-C AND CISPLATIN AGAINST GASTRIC-CANCER CELLS IN-VITRO

The synergistic antitumor activity of mitomycin C (MMC) and cisplatin (DDP) against the gastric cancer cell lines MKN-28 and MKN-45 was asse ssed in vitro using the MTT assay. The synergism of the two agents was evaluated in terms of the interaction index (I.I). The sequence of MM C followed by DDP showed higher antitumor activity than the reverse se quence against MKN-28 and MKN-45, and the intracellular concentration of platinum was significantly increased in MKN-45 by preincubation wit h MMC, suggesting that MMC modulates cellular permeability to DDP or t he ability of DDP to intercalate DNA. Since these two antitumor agents show different types of toxicity clinically, i.e., myelotoxicity by M MC and nephrotoxicity by DDP, this combination chemotherapy could be a dvantageous by providing synergistic antitumor activity without increa sed toxicity. (C) 1993 Wiley-Liss, Inc.