Rezisztenciamódosítók összehasonlítása multidrog-rezisztens prosztata-, egérlymphoma- és vastagbélrák-sejtvonalakon

Abstract

Introduction: The reason for unsuccessful tumor chemotherapy is related to multidrug resistance. An important factor is the overexpression of efflux pumps, such as P-glycoprotein. Aim: Amino- and amide-substituted steroid compounds and phenothiazine derivatives were investigated in tumor models in vitro. Method: The inhibition of P-glycoprotein was evaluated by flow cytometry and the interaction of these compounds with doxorubicin was investigated as well. Molecular docking was used to estimate the binding energies of the compounds to P-glycoprotein. Results: The aminosteroids showed anticancer activity on multidrug resistant mouse T-lymphoma and prostate cancer cell lines. The combination of steroids and doxorubicin potentiated its effect in hormone resistant prostate cancer cells. Among the N-hydroxyalkyl-2-aminophenothiazines, secondary amines exhibited anticancer effects on multidrug resistant colon adenocarcinoma cells. Conclusions: The tested phenothiazine and steroid derivatives showed potent anticancer activity, furthermore, the stereoisomerism of thioridazine did not play a role in the antitumor properties. Neither steroids nor thioridazine influenced apoptosis in hormone resistant cells. Orv. Hetil., 2016, 157(37), 1489–1495.