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多药耐药(multidrug resistance,MDR)是导致化疗失败的重要原因,多药耐药基因(multidrug resistance gene,mdr1)产物P-糖蛋白(P-glycoprotein,P-gp)过表达是最主要的耐药机制。原癌基因c-fos在肿瘤MDR中的作用渐受重视。主要选用人乳腺癌敏感株MCF-7和阿霉素(adriamycin,ADR)筛选的、mdr1/P-gp高表达的耐药株MCF-7/ADR,探讨c-fos在P-gp介导的乳腺癌MDR中的作用。相对于MCF-7,c-fos在MCF-7/ADR高表达。采用shRNA法下调c-fos表达后,MCF-7/ADR对ADR的敏感性大大增强,且mdr1/P-gp表达减少、P-gp外排功能降低。c-fos表达下调可逆转对P-gp介导的乳腺癌MDR的实验结果,为c-fos成为逆转肿瘤耐药诊断和治疗的新靶标,对实现耐药乳腺癌的分子靶向治疗提供了理论基础。
Multidrug resistance (MDR) is an important cause of chemotherapy failure. Overexpression of the multidrug resistance gene (mdr1) P-glycoprotein (P-glycoprotein) is the most important Resistance mechanism. The role of proto-oncogene c-fos in tumor MDR has received increasing attention. To investigate the effect of c-fos on P-gp-mediated ADF in MCF-7 / ADR cells, we selected MCF-7 and ADR-resistant mdr1 / P-gp- Role of breast cancer MDR. C-fos is highly expressed in MCF-7 / ADR relative to MCF-7. After down-regulating the expression of c-fos by shRNA, the sensitivity of MCF-7 / ADR to ADR was greatly enhanced, the expression of mdr1 / P-gp was decreased, and the efflux function of P-gp was decreased. Down-regulation of c-fos can reverse the experimental results of P-gp-mediated MDR in breast cancer and provide c-fos a new target for reversing the diagnosis and treatment of drug resistance in breast cancer, providing molecular targeted therapy for resistant breast cancer Theoretical basis.