Cross-resistance to antineoplastic agents in a human small-cell lung-cancer subline resistant to okadaic Acid.

We report on a human small cell lung cancer subline (H69/OA100) resistant to okadaic acid, an inhibitor of protein phosphatases. H69/OA100 showed cross-resistance to cis-diamminedichloroplatinum(II) (CDDP), adriamycin, and vinca alkaloids. Intracellular retention of adriamycin and CDDP in H69/OA100 was the same as those in H69. H69/OA100 was not shown to express MDR-1 by the reverse transcription polymerase chain reaction method. Expression level of mRNA of multidrug resistance-associated protein (MRP) in H69/OA100 was the same as that in H69. These data suggest that the mechanism of drug resistance in H69/OA100 might be due to a new mechanism of non-P-glycoprotein mediated multidrug resistance.