THE MULTIDRUG-RESISTANCE PHENOTYPE - MORP HOLOGICAL AND BIOLOGICAL FEATURES, EXCLUDING THE EFFLUX PUMP

Recent data from the literature together with personal results strongl y suggest that multidrug resistance phenotype is overwhelming the sole expression of P170 glycoprotein efflux pump. Morphological alteration s have been put in evidence in MDR cells after transmission and scanni ng electron microscopy. They include presence of osmiophilic vesicles and modifications of nuclear and nucleolar chromatin. Biological chara cteristics include the hypersecretory pattern of lysosomal enzymes fro m MDR cells. Such a fact could be more or less related to the increase d occurrence of mdr1 RNA in metastasis, especially in breast cancers, compared to primary tumors. If the P170-mediated efflux is one of the key mechanism of MDR, a decreased influx of anticancer drugs cannot be excluded. Liposomes, for instance made of cardiolipine, are thus able to increase the intracellular drug uptake of vinblastine without any action upon efflux mechanism.