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ATTEMPTS TO INFLUENCE THE DRUG RESISTANCE OF TUMOR CELLS IN EXPERIMENTAL SYSTEM
Aim: Analysis of two approaches to the problem of multidrug resistance management in the course of tumor treatment by working out an experimental model relevant to clinical research. Methods: Four cell sublines resistant to widely used cytostatics taxotere (Tax) or vincristine (Vcr) were developed by long-term culturing of the parental lymphoblastoid cell line IM-9 with incremental doses of these drugs. Constant presence of cyclosporin A (CsA) as a P-glycoprotein (Pgp) blocker in some cell cultures simulated prophylactic inhibition of this protein activity for prevention of drug resistance development from the very beginning of treatment. Both types of resistant cell sublines (developed in the presence or absence of cyclosporin A) were undergone to the action of the same Pgp blocker and drug inducing agents in short time cultures. Pgp activity by flow cytometry with fluorescence dye retention was checked and cytotoxicity assay by MTT-test was performed for drug resistance. Results: According to the experimental data obtained drug resistance prophylactics policy is problematically effective in prevention of tumor cells resistance to cytostatics. However, the attempts to influence drug resistance by Pgp pharmacologic blockade since it developed are much less benefit in case of the preceding preventive treatment.
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