肿瘤的发生发展是其炎性微环境“阴阳失衡”的恶性循环过程。中药紫草具有消炎抗癌功效，而其活性成分的作用机制尚不明确。前期研究表明紫草抗肿瘤活性成分为紫草素，可显著抑制炎症介质COX-2表达，表现出良好的抗肿瘤作用。因此，本项目采用现代药理学与分子生物学手段，研究紫草素通过NF-κB/COX-2通路抑制炎症反应，扭转微环境“阴阳失衡”，抑制结肠癌生长的分子机制；利用RNA_seq以及基因编辑技术，阐明紫草素抗结肠癌的分子机理—阻断IKKβ/NEMO缔合；运用蛋白重组、点突变、Biacore、小分子与蛋白共结晶以及计算化学方法，解析紫草素与IKKβ/NEMO相互作用规律以及位点。本项目结合化学生物学、结构生物学以及转录组学方法，系统阐明中药紫草活性成分通过阻断IKKβ/NEMO缔合，逆转结肠癌微环境炎症反应“阴阳失衡”，发挥抗肿瘤作用的分子机制，为中药紫草临床抗肿瘤应用提供科学依据。

The occurrence and development of tumor is a vicious cycle of "Yin-Yang Imbalance" in its inflammatory microenvironment. The traditional Chinese medicine Lithospermum has anti-inflammatory and antitumor effects, while the target of its active ingredients remains unclear. The previous study showed that the antitumor active ingredient of Lithospermum was shikonin, which could significantly inhibit the expression of inflammatory mediator COX-2 and exhibit excellent antitumor effects. Therefore, pharmacology and molecular biology methods were adopted in the present project to investigate the molecular mechanism of shikonin inhibiting inflammatory through NF-κB/COX-2 pathway, reversing the " Yin-Yang imbalance " in the microenvironment, and suppressing the growth of colon cancer. Next, the molecular mechanism (attenuating IKKβ/NEMO association) of shikonin against colon cancer would be elucidated by using RNA_seq and gene editing technology. Meantime, by means of protein recombination, point mutation, biacore, co-crystallization of small molecule and protein, and chemical calculation, the law, mode and site of interaction between shikonin and IKKβ/NEMO would be also analyzed. Finally, combined with chemical biology, structural biology and transcriptome, the present project will systematically elucidate the molecular mechanism of shikonin, the active ingredient of Lithospermum, by attenuating the IKKβ/NEMO association, reversing the "Yin-Yang imbalance" of inflammatory in the microenvironment of colon cancer, and demonstrating the anti-tumor effects. It would provide the scientific basis for the clinical antitumor application of the traditional Chinese medicine Lithospermum.