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ABSTRACT
Multidrug resistance (MDR) represents a major hindrance to the efficacy of cancer chemotherapeutics. While surgical resection, radiation, and chemotherapy can be used to reduce tumor size, the subsequent appearance of drug resistant cells is a frequent problem. One of the main contributors to the development of MDR is increased expression of multi-drug resistant protein 1 (MDR1), also known as P-glycoprotein (P-gp). P-gp is a membrane-associated efflux pump that can efficiently remove internalized taxane-base chemotherapeutics thus preventing drug accumulation and maintaining cellular viability. Consequently, investigation into the molecular mechanisms responsible for regulation of P-gp expression is necessary to facilitate treatment of MDR tumors. Using molecular and biochemical approaches, we identified that the micro-RNA, miRNA149, contributes to the development of MDR within malignant mesothelioma cells by regulating the expression of MDR1.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors acknowledge and thank Dr. Robert A. Holton (Florida State University Research Foundation, Tallahassee, FL) for supporting this study and providing Paclitaxel and its analog Simotaxel. DARZ was partially supported by Genentech Grant G-47608 while submitting this manuscript.