从干预有氧糖酵解的角度探讨丹参通过活血化瘀治疗肺癌的药理机制

无论缺氧与否，糖酵解均为肿瘤细胞优先选择的能量代谢途径，即有氧糖酵解，其在肿瘤的发生发展和诱导药物耐受中具有重要作用，现已成为癌症治疗的新靶点。中医认为“气”与能量密切相关，癌症多为“脏腑亏损、气虚统摄无权而生血瘀”。研究表明血瘀证型的癌症患者葡萄糖代谢率更高。我们推测肿瘤细胞低效率产能的有氧糖酵解代谢方式与中医的“气虚血瘀”之间必然存在联系；活血化瘀代表中药丹参可通过调控有氧糖酵解水平使肺癌细胞无法适应乏氧环境而死亡以治疗肺癌。本课题拟通过系统的细胞及动物实验分析丹参对肺癌细胞有氧糖酵解水平的影响；研究有氧糖酵解在丹参抗肺癌中的作用；并联合代谢组学技术、生物信息学手段和分子生物学方法阐明丹参干预有氧糖酵解的分子机制。本项目旨在通过深度解读丹参“活血化瘀”防治肺癌的现代科学内涵，探索中医理论和西医科学之间的内在联系，是中西医结合的一次创新性尝试。

Glycolysis is the main pathway of tumor cells to produce energy even oxygen exists, which called aerobic glycolysis. Glycolysis could survive cancer cells from hypoxia during tumorigenesis and induce chemoresistance, which makes it became a new target for cancer therapy. “blood stasis” exists in most cancer patients because “Qi is deficiency and unification of the blood”. “Qi” refers the nutrients and the energy. Therefore, aerobic glycolysis resulting energy deficiency supposed to be one of the causes to induce “blood stasis” in cancer patients. Besides, as a classic “huo xue hua yu” herbs, Danshen could reverse the glycolysis which makes lung cancer cells cannot adapt to the hypoxic environment and die. This is the hypothesis in the study. To confirm it, cell lines and model animals are operated to figure out the effects of Danshen on the glycolysis in lung cancer cell and the role of aerobic glycolysis in Danshen’s pharmacologic function during lung cancer treating. Metabolomics test, bioinformatic analysis, and molecular biologic array are used to study the mechanism of Danshen regulates the aerobic glycolysis in lung cancer cell. In this project, the purpose of the study on the Danshen’s pharmacologic mechanism is to discover the intrinsic relation between traditional medicine theory and modern scientific connotation. It is an innovative attempt to integrate traditional Chinese medicine and Western medicine.