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| Effects of c-fos Down-regulation via shRNA on P-gp-mediated Multidrug Resistance in Human Breast Cancer MCF-7/ADR Cells |
| SHI Rui-zan, HU Xiao-ling, FAN Yan-ying |
| Shanxi Medical University, Taiyuan 030001, China |
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Abstract Multidrug resistance (MDR) is the main reason of chemotherapy failure. The overexpression of P-glycoprotein (P-gp), encoded by the multidrug resistance (mdr1) gene, is thought to be the major cause of MDR phenotype. Since much attention has been paid to the role of proto-oncogene c-fos in MDR, adriamycin (ADR)-selected resistant breast cancer cells (MCF-7/ADR) with mdr1/P-gp overexpression and parental drug-sensitive cells (MCF-7) were chosen to analyze the role of c-fos in P-gp-mediated MDR. Elevated c-fos expression is observed in MCF-7/ADR compared to MCF-7 cells. Down-regulation of c-fos expression via shRNA resulted in sensitization of MCF-7/ADR cells to ADR and decreased the expression of mdr1/P-gp and efflux function of P-gp. Based on these results, c-fos may represent a potential molecular target for resistant cancer therapy, and suppressing c-fos gene expression may therefore be an effective means for targeted molecular therapy.
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Received: 29 August 2012
Published: 25 December 2012
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