EFFECT OF PENTOXIFYLLINE ON P-GLYCOPROTEIN MEDIATED VINCRISTINE RESISTANCE OF L1210 MOUSE LEUKEMIC-CELL LINE

Effect of pentoxifylline (PTX) on vincristine (VCR) resistance of mult idrug resistant L1210/VCR mouse leukemic cell line was studied. Revers al effect of PTX (in concentration 50-150 mg/l) on vincristine resista nce, i.e. potentiation of vincristine cytotoxicity on L1210/VCR cells by PTX was found. PTX alone in the above concentration did not exert a ny significant cytotoxic effect on sensitive or resistant cell lines i n the absence of vincristine. Resistance of L1210/VCR cell line was fo und previously to be accompanied with overexpression of drug transport ing P-glycoprotein. Indeed, lower level of H-3-vincristine accumulatio n by resistant L1210/VCR cell line In comparison with sensitive 1,1210 cell line was observed. Accumulation of 3H-vincristine by L1210/VCR c ell line was significantly increased in the presence of PTX. PTX in th e same condition did not exert any considerable effect on accumulation of H-3-vincristine by nonresistant L1210 cells. Observable morphologi cal damage was observed in L1210/VCR cells cultivated in medium contai ning vincristine (0.2 mg/l) and pentoxifylline (100 mg/l) in compariso n with the non-damaged cells in the presence of vincristine or pentoxi fylline alone. The results obtained indicate that pentoxifylline may b e considered as a reversal agent in multidrug resistance.