Accumulation of chlorine e6 derivatives in cells with different level of expression and function activity of multidrug resistance protein P-gp 170

This work deals with studying the influence of overexpression and function activity of multidrug transporter protein P-gp 170 on the intracellular accumulation of several porphyrin sensitizers, including chlorin e6 (Chl e6), di- (DME) and trimethyl esters (TME) of Chl e6. A parental IM9 cell line and two IM9 drug-resistant IM9 sublines were used. With flow cytometry technique the rates of chlorines accumulation in different IM9 cells and values were related to the extent of multidrug resistance (MDR) phenotype. Using P-gp 170-specific antibodies and fluorescent probe JC-1 an increased expression and function activity of P-gp 170 was detected for drug-resistant cells. It was obtained that drug-resistant IM9 cells accumulated chlorines to a lesser extent than the respective wild type, however the differences did not exceed 30%. Verapamil, cyclosporine, known to reverse the MDR phenotype affects equally IM9-Vinc IM9-Tax and Im9 cells. Our results demonstrate that the P-gp 170 does not appear to play a role in the intracellular accumulation of chlorines. Since the enhanced activity of P-gp 170 in tumor cells is a factor of their resistance to the action of various antitumor drugs, we conclude that photodynamic therapy could be useful in killing cells exhibiting the MDR.