Modulation of the multidrug resistance (MDR) phenotype in CEM MDR cells simultaneously exposed to anti HIV-1 protease inhibitors (PI's) and cytotoxic drugs.
Vinblastine, vincristine and doxorubicyn are currently used in chemotherapeutic treatments of several malignancies including HIV-1 associated tumours Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL). Hence, AIDS patients also affected by KS and NHL may be simultaneously subjected to highly active antiretroviral therapy (HAART) and cytotoxic drugs to combat HIV-1 infection and cancer aggressiveness. In order to assess if the combination of these therapies may affect cell growth and survival of P-glycoprotein expressing MDR variants of the human CD4+ T-lymphoblastoid CEM cell line, the protease inhibitors (PI's) ritonavir, saquinavir and indinavir were tested in an in vitro assay for their ability to potentiate the vinblastine, vincristine and doxorubicyn cytotoxicity. The results we obtained demonstrated that at the concentration of 10 micrograms/ml, ritonavir and in a lesser extent saquinavir act as MDR reversing agents. By contrast, the PI indinavir at least in the CEM cell system, does not affect the patterns of drug resistance. The level of chemosensitization exerted by ritonavir and saquinavir suggests that these PI's may render P-glycoprotein expressing MDR cells de novo susceptible to the antineoplastic drugs vinblastine, vincristine and doxorubicyn.
Dupuis
Maria Luisa
ML
Laboratorio di Immunologia, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma. mldupuis@iss.it
Tombesi
Marina
M
Cianfriglia
Maurizio
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016333:HIV Protease; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017320:HIV Protease Inhibitors; D016333:HIV Protease