Effect of phorbol myristate acetate (PMA) on P-glycoprotein mediated vincristine resistance of L1210 cells

Abstract

Effect of phorbol myristate acetate (PMA) on P-glycoprotein (P-GP)-mediated vincristine resistance of the multidrug resistant mouse leukemic cell line L1210/VCR was studied by one hour lasting incubation of cells in the presence of PMA, and after three days of cultivation in the presence of the same substance. After the incubation with 100 micrograms.1-1 PMA the accumulation of [3H]-vincristine by the above cells was significantly depressed. Moreover, full reverse of verapamil-induced stimulation of [3H]-vincristine accumulation was observed in the presence of PMA. In contrary, when cells were cultivated three days in the presence of PMA, only slight but non-significant increase of [3H]-vincristine accumulation was observed. Slight increase of vincristine accumulation by cells cultivated in the presence of PMA was also supported by higher sensitivity of these cells to vincristine.