Induction of the multidrug-transporter P-glycoprotein by 3'-azido-3'-deoxythymidine (AZT) treatment in tumor cell lines.
A major form of multidrug resistance, which represents a serious obstacle to the success of chemotherapy, is caused by the over-expression of MDR-1 gene encoded P-glycoprotein. The present investigation was aimed to determine whether AZT, a cytostatic agent that interferes with the human immunodeficiency virus replication, is able to induce MDR-1 expression in tumor cells. After a short term exposure of human lymphoblastoid cells to AZT MDR-1 P-glycoprotein was found in the treated cells. This ATP-dependent drug-efflux pump interferred with cytotoxic efficacy of anticancer drugs such as vinblastine. This phenomenon should be carefully considered during anti-viral and anti-tumoral combined chemotherapies in AIDS patients.
Signoretti
C
C
Institute of Virology, University La Sapienza, Rome, Italy.
Romagnoli
G
G
Turriziani
O
O
Antonelli
G
G
Dianzani
F
F
Cianfriglia
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D015215:Zidovudine; D014747:Vinblastine