中文摘要
放射治疗是鼻咽癌治疗的主要手段,而放射抗拒严重制约了其疗效,“益气活血养阴”法(生脉姜黄散)对鼻咽癌有放射增敏作用,但其分子机制尚不明了。我们前期承担的国家自然基金项目研究表明,射线诱导的CDK6低甲基化可能是放射抗拒的重要分子基础。体内实验证实生脉姜黄散有良好的放射增敏作用;体外实验发现并验证lncRNA及多个效应分子参与调控CDK6,其中一个lncRNA(NR_110088)可能介导调控CDK6基因启动子甲基化。因此提出NR_110088调控CDK6甲基化水平而逆转放射抗拒的可能性。本项目拟在细胞调控、动物模型及临床病例中探讨lncRNA/CDK6及效应分子与放射敏感性之间的关系,获得生脉姜黄散作用于lncRNA/CDK6相关信号通路并逆转放射抗拒的可靠证据,为诠释鼻咽癌放射抗拒及益气活血养阴法放射增敏的分子机制、应用中药多靶点辅助治疗肿瘤提供有力的科学依据。
英文摘要
Radiotherapy is the main treatment of nasopharyngeal carcinoma (NPC), but radiation resistance is severely restricting its efficacy.The traditional chinese medicine(TCM) Shengmaijianghuangsan,which is formed by the method of supplementing qi-activating blood circulation and nourishing yin, has radiosensitizing effects, but its molecular mechanism is still unknown. CDK6 is closely related with radiosensitivity of NPC through hypomethylation in our previous studies; It’s confirmed that Shengmaijianghuangsan has good radiosensitization effect In vivo. In vitro experiments found for the first time and validate lncRNAs and multiple effective molecules involved in regulating the CDK6, thus it put forward the possibility that lncRNA NR_110088 targetes CDK signal pathways and reverses the radioresistance through hypomethylation. This project aims at inquiring into the relationship between lncRNA/CDK6 and the radiation resistance in the cases of regulating cells, animal model and NPC cases ,and obtain the reliable evidence of Shengmaijianghuangsan acting on NR_110088 to targetedly regulate CDK6 hypomethylation and to reverse the radiation resistance. It can provide powerful scientific evidence to annotate the molecular mechanism of NPC radioresistance and Shengmaijianghuangsan sensitizing, the application of TCM in cancer treatment and the lncRNA in multi-target therapeutic of cancer.
