非小细胞肺癌是常见恶性肿瘤，其治疗一直是现代西方医学研究的难点。中西医结合治疗方式是我国肿瘤领域的特色疗法。申请人前期研究发现，扶正固本类中药女贞子活性成分齐墩果酸对非小细胞肺癌有显著抗肿瘤作用，而AURKA是非小细胞肺癌的关键治疗靶点。本项目在前期工作基础上，利用中医药学、肿瘤学和分子生物学多学科交叉技术，构建中药小分子齐墩果酸诱导型CRISPR/dCas9转录调控系统COTIS，明确该方法对AURKA表达的抑制作用，阐明齐墩果酸联合COTIS系统对于肿瘤细胞增殖、凋亡、迁移和侵袭能力的影响，并在裸鼠荷瘤模型中验证该方法对于非小细胞肺癌的治疗作用。该研究能够增强齐墩果酸的抗肿瘤效果，有望解决基因编辑系统精准调控与非小细胞肺癌治疗的难题，为临床中西医结合治疗非小细胞肺癌奠定理论和实践基础。

Non-small cell lung cancer (NSCLC) is a common malignant tumor, and its treatment remains challenging. The combination of traditional Chinese and Western medicine is a characteristic tumor therapy in China. In the previous study, we found that oleanolic acid, the active component of Ligustrum lucidum, has a significant anti-tumor effect on NSCLC. And AURKA is a crucial target in the treatment of NSCLC. Based on the previous work, we constructed a CRISPR/dCas9-inspired Oleanolic Acid-induced Transcription Inhibition System (COTIS) which is an interdisciplinary research of Chinese medicine, oncology and molecular biology. Then we explore its inhibition effect on AURKA, clarify the effect of COTIS with oleanolic acid on the proliferation, apoptosis, migration and invasion of NSCLC cells. Therapeutic effect of COTIS on NSCLC in nude mice bearing tumor is further verified. This system can enhance the antitumor effect of oleanolic acid, and solve the problem of precise regulation of gene editing system in the treatment of NSCLC, thus provide a theoretical and practical foundation for the treatment of NSCLC with the combination of traditional Chinese and Western Medicine.