摘要
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 the main reason of chemotherapy failure. The overexpression of P-glycoprotein （P-gp）, encoded by the multidrug resistance （mdrl） gene, is thought to be the major cause of MDR phenotype. Since much attention has been paid to the role of proto-oncogene c-los in MDR, adriamycin （ADR）-selected resistant breast cancer cells （MCF-7/ADR） with mdrl/P-gp overexpression and parental drugsensitive 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 mdrl/P-gp and efflux function of P-gp. Based on these results, c-los 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.
出处
《中国生物工程杂志》
CAS
CSCD
北大核心
2012年第12期8-12,共5页
China Biotechnology
基金
国家青年基金资助项目(81202520)
关键词
C-FOS
多药耐药
P-糖蛋白
分子靶向治疗
c-fos Multidrug resistance （MDR） P-glycoprotein （P-gp） Targeted molecular therapy
