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Modulation of MDR1 and MRP3 Gene Expression in Lung Cancer Cells after Paclitaxel and Carboplatin Exposure
Institute of Biopathology and Regenerative Medicine (IBIMER), Department of Anatomy and Human Embryology, School of Medicine, University of Granada, Granada E-18071, Spain
Service of Medical Oncology, Virgen de las Nieves Hospital, Granada E-18012, Spain
Department of Health Science, University of Jaén, Jaén E-23071, Spain
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 28 September 2012; in revised form: 20 November 2012 / Accepted: 26 November 2012 / Published: 5 December 2012
Abstract: Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.
Keywords: lung cancer; resistance; MDR; MRP; paclitaxel; carboplatin
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Melguizo, C.; Prados, J.; Luque, R.; Ortiz, R.; Caba, O.; Álvarez, P.J.; Gonzalez, B.; Aranega, A. Modulation of MDR1 and MRP3 Gene Expression in Lung Cancer Cells after Paclitaxel and Carboplatin Exposure. Int. J. Mol. Sci. 2012, 13, 16624-16635.
Melguizo C, Prados J, Luque R, Ortiz R, Caba O, Álvarez PJ, Gonzalez B, Aranega A. Modulation of MDR1 and MRP3 Gene Expression in Lung Cancer Cells after Paclitaxel and Carboplatin Exposure. International Journal of Molecular Sciences. 2012; 13(12):16624-16635.
Melguizo, Consolación; Prados, Jose; Luque, Raquel; Ortiz, Raúl; Caba, Octavio; Álvarez, Pablo J.; Gonzalez, Beatriz; Aranega, Antonia. 2012. "Modulation of MDR1 and MRP3 Gene Expression in Lung Cancer Cells after Paclitaxel and Carboplatin Exposure." Int. J. Mol. Sci. 13, no. 12: 16624-16635.