基于Wnt/TCF7-ceRNA调控网络探讨麦门冬合千金苇茎汤抗肺癌的分子机制

麦门冬合千金苇茎汤（金方）是国医大师周仲瑛教授“痰瘀郁毒，气阴两虚”理论指导下，经长期临床治疗肺癌的有效经验方。.前期临床研究已证实“痰瘀郁毒，气阴两虚”在临床中客观存在及该方抗肺癌的疗效。实验研究则发现，金方可通过抑制Wnt/TCF7通路来影响肿瘤的生长，并初步筛选出其上游的miRNAs。.本项目以前期研究为基础，以“痰瘀郁毒，气阴两虚”病机理论为主导思想，遵循中医学自身特点，从基因上游调控分子lncRNA入手，运用LncPathTM芯片技术，获得与肺癌及金方相关的lncRNA表达谱；对筛选出的差异lncRNA进行qRT-PCR验证和生物信息学分析，并对关键靶基因和信号通路进行体内外验证；构建与肺癌及金方疗效密切相关lncRNA-miRNA-mRNA即ceRNA调控网络，进一步揭示该方抗肺癌作用机制，诠释“痰瘀郁毒，气阴两虚”理论内涵，为中医药抗肿瘤研究提供新思路。

Maimendong and Qianjinweijing formula (Jin formula) is an effective anti-lung cancer prescription that has been tested by long-term clinical practice under the guidance of Professor Zhou Zhongying’s “phlegm-stasis stagnating the lung and impairment of dual yin and qi” theory..Previous clinical studies have demonstrated that phlegm-stasis and cancerous toxin exist objectively in tumor clinical syndrome and Jin formula has remarkable anti-lung cancer effects. Experimental studies have shown that this prescription could affect tumour growth by inhibition of Wnt/TCF7 pathway, and the related upstream miRNAs have also been selected..Based on previous studies, with “phlegm-stasis stagnating the lung and impairment of dual yin and qi” pathogenesis theory as the dominant thought, the project follows traditional Chinese medicine’s (TCM’s) own characteristics, starts from the upstream regulatory molecules of genes－long noncoding RNAs　(lncRNAs), and collects lncRNA expression profiling data closely related with lung cancer and Jin formula by the application of LncPathTM chip technology. To prove the accuracy of differently expressed miRNAs and to verify the functions of key target genes and signaling pathways, we adopt qRT-PCR methods, bioinformatics analysis and experimental studies both in vitro and in vivo. Finally, we construct the lncRNA-miRNA-mRNA, also known as competing endogenous RNAs（ceRNA）regulation network. All these will contribute to the exploration of the anti-lung cancer mechanism of this prescription and interpretation of “phlegm-stasis and cancerous toxin” pathogenesis theory, and thus provide new important ideas for anti-lung cancer research of TCM.