期刊
CURRENT PHARMACEUTICAL DESIGN
卷 10, 期 6, 页码 647-657出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612043453117
关键词
cyclooxygenase-2; prostaglandins; P-glycoprotein; multidrug resistance; MDR1; renal mesangial; apoptosis; chemotherapeutic agents
资金
- NHLBI NIH HHS [HL 22563] Funding Source: Medline
- NIDDK NIH HHS [DK 41684] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL022563, R37HL022563] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK041684] Funding Source: NIH RePORTER
Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major obstacle for the succesfull chemotherapy. One of the causes of the development of cellular resistance to a wide variety of drugs is the elevated expression of membrane transporter proteins such as members of ATP binding cassette (ABC) protein superfamily. Expression of the ABC transporter MDR1, also termed P-glycoprotein (P-gp), seems to correlate with drug resistance of tumors to chemotherapy. Cyclooxygenase-2, an inducible isoform of enzyme, responsible for generation of prostaglandins from arachidonic acid, is constitutively expressed in a number of cancer cells. Anti-cancer potency of cyclooxygenase inhibitors is established, but the mechanism of Cox-2-dependent potentiation of tumor growth is a subject of intense discussion. Here we focus on the discussion of potential link between Cox-2 expression and development of multidrug resistance phenotype. Our observation, that enforced expression of Cox-2 causes enhancement in MDR1 expression and functional activity suggests the existence of causal link between Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to decrease function of MDR1 may enhance accumulation of chemotherapy agents and decrease resistance of tumors to chemotherapeutic drugs.
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