P-glycoprotein expression by cancer cells affects cell cytotoxicity and cell-cycle perturbations induced by six chemotherapeutic drugs

Background: P-glycoprotein (P-gp)–mediated chemoresistance plays an important role in drug resistance. Methods: We investigated if P-gp expression by cancer cells affects cell cytotoxicity and cell-cycle perturbations induced by six commonly used chemotherapeutic agents (doxorubicin, daunorubicin, mitoxantrone, vinblastine, paclitaxel, and colchicine). For this purpose, we used KB cell lines as a model and flow cytometric cell viability and drug-induced cell-cycle perturbation–based methods. We continuously cultured KB cell lines, in the presence of various anticancer agents and measured the cell-cycle kinetics and percentage of cell viability by flow cytometry at different time intervals. Results: The highly resistant cell line KB V-1 was significantly less susceptible to drug cytotoxicity than the sensitive cell line KB 3-1. KB V-1 cells cultured with different chemotherapy agents continued cell-cycle progression without any significant perturbation of cell compartment distribution. Addition of verapamil, by inhibiting P-gp, reversed resistance thereby increasing drug cytotoxicity and allowing the appearance of drug induced cell-cycle perturbations. Conclusions: We conclude that P-gp interferes with cell cytotoxicity and cell-cycle perturbations induced by anticancer agents. Flow cytometry can be used to conveniently detect P-gp–mediated chemoresistance by cancer cells as it allows the analysis of cell cytotoxicity and cell-cycle modifications after exposure to specific chemotherapeutic and reversal agents.