Todor I. The role of lipids in development and modulation of drug resistance of tumor cells

Thesis is dedicated to the actual problem in oncology – determination the role of lipids in mechanisms of drug resistance development in tumor cells and provement of the ways for membrane lipid profile modification for elevation of cytostatic effects. We showed in vitro and in vivo that development of drug resistance phenotype is accompanied by increase in cholesterol, phosphatydylserine, sphingomyelin, and decrease in phosphatydylcholine, phosphatydyle- thanolamine and their desaturation in tumor cell membranes (more than by 22%, p<0.05). We observed that during development of drug resistance the mitochondrial oxidative phos- phorylation intensity and activity of all NADPH-producing enzymes, as well as glutathione reductase, glutathione S-transferase, glutathione peroxidase and catalase significantly increased (more than by 45%, p<0.05). In vivo we proved the need to use liposomal forms of cytostatics and ferromagnetic cisplatin-containing nanocomposite for modulation of tumor drug resistance. We showed that one of the mechanisms of action of liposomal forms of cytostatics and ferromagnetic nanocomposite is associated with structural and functional changes in cell membranes, resulting in decrease of its microviscosity, 44 causing more intensive uptake of the drug by cells and increase of its intracellular concentration.