Li Yun-Ling, Zhao Yi-Gang, Chen Bin, Li Xiao-Feng
Pharmazie. 2016 Dec 1;71(12):715-718. doi: 10.1691/ph.2016.6764.
Chemoresistance in cancer is one of the major hindrances in cisplatin (DPP) treatment for nasopharyngeal carcinoma (NPC). The mechanism of such resistance remains unknown. Therefore, the present study aimed to clarify the mechanism of DDP resistance and attempted to reduce chemoresistance. Here, we found that miR-132, as a tumor suppressor, was poorly expressed in a cisplatin resistant CNE2 cell line (CNE2/DPP) accompanied with a decreased expression of miR-132 and an increased expression of FOXA1 compared with the parental cells CNE2. Exogenous overexpression of miR-132 in CNE2/DPP could sensitize their reaction to the treatment of cisplatin. In addition, FOXA1 knockdown in CNE2/DPP cells increased the chemosensitivity to DPP, suggesting the dependence of FOXA1 regulation in miR-132 activity. Moreover, miR-132 can restore cisplatin treatment response in cisplatin-resistant xenografts in vivo, while FOXA1 protein levels were decreased. In summary, our results provide novel mechanistic insights into the role of miR-132/FOXA1 signaling in the cisplatin resistance of NPC cells. Targeting of miR-132 is a potential therapeutic approach for NPC.
癌症中的化疗耐药性是顺铂（DPP）治疗鼻咽癌（NPC）的主要障碍之一。这种耐药性的机制尚不清楚。因此，本研究旨在阐明顺铂耐药的机制，并试图降低化疗耐药性。在这里，我们发现，作为一种肿瘤抑制因子，miR-132在顺铂耐药的CNE2细胞系（CNE2/DPP）中表达较低，与亲本细胞CNE2相比，miR-132表达降低，FOXA1表达增加。在CNE2/DPP中，外源性过表达miR-132可使其对顺铂治疗的反应敏感。此外，在CNE2/DPP细胞中敲低FOXA1可增加对DPP的化疗敏感性，这表明FOXA1调节依赖于miR-132活性。此外，miR-132可以恢复体内顺铂耐药异种移植瘤对顺铂治疗的反应，同时FOXA1蛋白水平降低。总之，我们的结果为miR-132/FOXA1信号通路在NPC细胞顺铂耐药中的作用提供了新的机制性见解。靶向miR-132是NPC的一种潜在治疗方法。
