Department of general surgery, The Second Affiliated Hospital of Wenzhou Medical College, China.
Acta Biochim Biophys Sin (Shanghai). 2010 Dec;42(12):900-7. doi: 10.1093/abbs/gmq094. Epub 2010 Oct 27.
Overexpression of multidrug resistance 1 (MDR1) in cancer remains one of the major causes for the failure of chemotherapy. In the present study, we found that MyoD and PEA3 could activate P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. MyoD or PEA3 could bind to the E-box and PEA3 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by MyoD and PEA3 may provide potential ways to overcome MDR in cancer treatment.
多药耐药 1(MDR1)在癌症中的过度表达仍然是化疗失败的主要原因之一。在本研究中,我们发现 MyoD 和 PEA3 可以激活 SGC7901 细胞中的 P 糖蛋白(P-gp)表达。MyoD 和 PEA3 的敲低减弱了 MDR1 的表达,并增加了 SGC7901/VCR 细胞中由 P-gp 转运的多药耐药癌细胞对细胞毒药物的敏感性。MyoD 或 PEA3 可以与 MDR1 启动子上的 E-box 和 PEA3 位点结合,并激活其转录。MyoD 和 PEA3 对 MDR1 表达的调节可能为克服癌症治疗中的多药耐药提供潜在途径。