鼻咽癌是我国常见的肿瘤之一，由于肿瘤细胞对药物治疗的不敏感给临床治疗带来巨大的困难，并导致肿瘤患者存活率较低。课题组前期研究结果表明，鼻咽癌细胞对顺铂等药物治疗的敏感性降低与其激活ERK及Akt信号通路有一定的联系，且发现miR-768-3p的水平明显增高，抑制miR-768-3p及翻译起始因子eIF4E的变化，在鼻咽癌的耐药中发挥了重要的作用。本项目拟对P53-miR-768-3p-eIF4E在鼻咽癌对顺铂耐药中的作用进行研究，探讨抑制miR-768-3p增强鼻咽癌细胞对顺铂诱导凋亡敏感性的分子机制；并进一步阐明eIF4E及P53的作用。探讨与鼻咽癌治疗不敏感形成密切相关的靶信号，从而破解鼻咽癌细胞化疗抗药性的机制，并寻找提高其对化疗药物敏感性的策略。本研究对于探索鼻咽癌治疗新靶点、设计新的治疗用药和提升化疗药物的抗肿瘤疗效有着重要意义，并为其他肿瘤研究提供参考。

Nasopharyngeal carcinoma is one of common tumor in our country, due to the tumor cells is not sensitive to the drug treatment, which bring huge difficulties, and lead to low survial rat in clinical treatment.Preliminary data from our lab showed that reduced susceptibility to cisplatin therapy in Nasopharyngeal carcinoma cell was related to the activation of ERK and Akt signaling pathways, and is accompanied by that miR-768-3p levels increased significantly, the inhibition of miR-768-3p and transcription factor eIF4E changes in nasopharyngeal carcinoma drug resistance plays an important role. This project intends to investigate the role of P53/miR-768-3p/eIF4E in cisplatin resistance in nasopharyngeal carcinoma, inhibition of miR-768-3p enhances sensitivity to cisplatin induced apoptosis of nasopharyngeal carcinoma cell molecular mechanism; And further clarify eIF4E, and the function of P53. Discussion is not sensitive with the treatment of nasopharyngeal carcinoma formation is closely related to the target signal, thus crack chemotherapy drug resistance mechanism of nasopharyngeal carcinoma cells, and find the strategies to improve its sensitivity to chemotherapeutic drugs.

摘要：本项目针对鼻咽癌对化疗及放疗敏感性降低的机制开展工作，研究通过收集临床鼻咽癌肿瘤标本，收集鼻咽癌细胞耐药细胞株，并在实验室诱导建立鼻咽癌耐药株，结果发现对化疗药物不敏感的鼻咽癌细胞株中多个miRNA的表达与敏感株相比存在具有统计学意义的明显差别。我们通过调控对顺铂敏感性不同的细胞株中miRNA的表达，检测鼻咽癌细胞株化疗后凋亡和增殖情况，发现miRNA在鼻咽癌细胞株化疗耐药中的作用。同时针对miRNA与肿瘤细胞凋亡之间开展研究，发现了在鼻咽癌细胞放疗及化疗的过程中，miRNA可影响鼻咽癌细胞对化疗药物诱导凋亡的敏感性。同时发现，在鼻咽癌的耐药细胞株中出现EMT现象及肿瘤细胞侵袭转移的明显改变。目前共发表与本项目直接相关论文36 篇，其中标注基金资助的的SCI论文11 篇，国内学术会议20余人次。课题组在保证原有研究计划顺利开展的前提下，积极的探讨肿瘤细胞能量代谢相关机制。课题按照申报设计顺利开展，并不断探寻解决新问题的方法和策略，为提高鼻咽癌临床治疗敏感性提供了思路。