EFFECT OF MULTIDRUG-RESISTANT P-GLYCOPROTEIN GENE-EXPRESSION ON CHLOROALUMINUM TETRASULFONATE PHTHALOCYANINE CONCENTRATION

The effect of multidrug-resistant P-glycoprotein gene expression (MDR1) in 3T3 cells on cellular concentrations and cytotoxicity induced by the photodynamic agent chloroaluminum tetrasulfonate phthalocyanine (AISPc) was evaluated. 3T3 cells transfected with a retroviral vector expressing human MDR1 cDNA were resistant to colchicine. Resistant cells incubated with daunomycin accumulated only 40-50% of the quantity of daunomycin accumulated in control cells. Resistant cells incubated with daunomycin in the presence of verapamil had intracellular daunomycin concentrations approximately equal to control cells without verapamil. When these MDR1 3T3 cells were incubated with AISPc, cellular concentrations of AISPc did not differ between cells resistant to colchicine and those that were not. Similarly, there was little difference in cytotoxicity demonstrated by Cromium-51 release in the two cell lines exposed to AISPc and light (675 nm; 6 J/cm2). This study suggests photodynamic therapy using AISPc may be a useful treatment modality for tumors in which the MDR1 P-glycoprotein confers resistance to cancer chemotherapeutics. (C), 1993 Wiley-Liss, Inc.