miR-487a增加MCF-7/MX荷瘤鼠对米托蒽醌敏感性机制探讨

The study of mechanisms of miR-487a on increasing the sensitivity of xenograft mice induced by MCF-7/MX cells to mitoxantrone(MX)

目的:研究miR-487a调控米托蒽醌(MX)耐药的乳腺癌耐药细胞MCF-7/MX荷瘤鼠对MX敏感性的作用与机制。方法:通过裸鼠腋窝皮下接种MCF-7/MX细胞构建荷瘤鼠模型;real-time RT-PCR、Western blot方法检测荷瘤鼠瘤体内注射miR-487aagmir后对移植瘤内miR-487a及BCRP表达的影响;并通过对荷瘤鼠尾静脉注射MX后移植瘤体积和瘤重的检测,研究miR-487a对MCF-7/MX荷瘤鼠药物敏感性的影响。结果:在MCF-7/MX细胞荷瘤鼠瘤体内注射miR-487aagmir诱导miR-487a表达增高约7倍;降低了移植瘤内的BCRP的mRNA和蛋白表达约30%;且显著降低了MX处理的MCF-7/MX细胞荷瘤鼠移植瘤的重量,即增加了对MX的敏感性。结论:miR-487a抑制了MCF-7/MX细胞荷瘤鼠的BCRP表达,增加其对米托蒽醌的敏感性。

Objective：To explore the action and mechanisms of miR-487 aon the sensitivity of xenograft mice induced by MCF-7/MX cells to MX.Methods：The xenograft mice were constructed by inoculating subcutaneously MCF-7/MX cells into the flank of nude mice.The expression of miR-487 aand breast cancer resistance protein（BCRP）in xenograft tumors induced by MCF-7/MX cells after injecting miR-487 aagmir were examined by real-time RT-PCR and Western blot analysis.The sensitivity of xenograft mice induced by MCF-7/MX cells to MX was analyzed by observing the changes of the tumor weight.Results：The intratumoral injections of miR-487 aagmir induced the increases of miR-487 aby 7fold,decreased the mRNA and protein expression of BCRP by 30%,and significantly reduced the tumor weight of the xenograft mice.Concluslon：miR-487 acan inhibit the expression of BCRP and increase the sensitivity of xenograft mice induced by MCF-7/MX cells to MX.