Difference in effects of alkyl-lysophospholipids and verapamil on vincristine transport in vincristine-sensitive and -resistant human myelogenous leukemia K562.

Several kinds of alkyl-lysophospholipids enhanced the accumulation of vincristine (VCR) in both drug-sensitive and -resistant K562 cells. The drugs also augmented the efflux of VCR from the tumor cells. It is assumed that alkyl-lysophospholipids made tumor cells permeable to both the influx and efflux of VCR. The alkyl-lysophospholipids produced nonspecific effects of almost equal intensity in both sensitive and resistant tumor cells. These effects were compared with those of verapamil, a calcium channel blocker. Verapamil, as reported previously, specifically inhibited the efflux of drugs from tumor cells, especially drug-resistant tumor cells, thereby enhancing the accumulation of antitumor agents in the cells. Thus the actions of alkyl-lysophospholipids and verapamil in tumor cells were obviously different. Furthermore, the combined effects of alkyl-lysophospholipids and verapamil were additive or synergistic, indicating that their sites of action may be different.