基于ROS/MAPK-Caspase-3/GSDME通路介导的细胞焦亡探讨复方肺力咳胶囊调控三阴性乳腺癌肿瘤免疫的作用机制和活性物质基础

三阴性乳腺癌是一种威胁全球女性健康的恶性肿瘤，具有高转移和高复发的特点，由于缺乏明确的治疗靶点，成为临床癌症治疗的一个难题。细胞焦亡是一种新发现的炎症细胞程序性死亡方式，与肿瘤发生密切相关。前期，我们证实贵州特色民族药肺力咳胶囊在体内外抑制三阴性乳腺癌的生长，诱导细胞焦亡并增强抗肿瘤免疫应答，但具体机制和活性物质基础不详。进一步研究发现，肺力咳胶囊能够调控ROS/MAPK和Caspase-3/GSDME通路，因此，我们推测肺力咳胶囊可能通过ROS/MAPK-Caspase-3/GSDME通路介导的细胞焦亡，调控三阴性乳腺癌肿瘤免疫应答，发挥抗三阴性乳腺癌的作用。本项目拟在动物-细胞-分子水平，并结合网络药理学和药物分离提取技术，探究肺力咳胶囊调控细胞焦亡的作用的活性物质基础和潜在靶点，为抗三阴性乳腺癌药物的研发提供科学理论依据，同时为地方特色中药复方制剂的创新和现代化发展提供新的研究思路。

Triple-negative breast cancer is a kind of malignant tumor with high metastasis and high recurrence that threatens the women's health worldwide. Because of the lack of clear treatment target, triple-negative breast cancer has become a difficult problem in clinic. Pyroptosis is a newly discovered inflammatory form of programmed cell death, which is closely related to tumorigenesis. Previously, we found that Feilike capsule, a Guizhou ethnic medicine, inhibited the tumor growth of triple-negative breast cancer, induced cell pyroptosis and enhanced the anti-tumor immune response in vivo and in vitro. However, the specific mechanism and active ingredients are unknown. Further investigation revealed that Feilike capsule could regulate ROS/MAPK and Caspase-3/GSDME pathway. We speculated that Feilike capsule may regulate the tumor immune response and exert its anti-tumor activity through ROS/MAPK and Caspase-3/GSDME pathway-mediated cell pyroptosis in triple negative breast cancer. In this study, we aimed to explore the active ingredients and potential targets through which Feilike capsule induced cell pyroptosis using cell function assays and animal model in combination with network pharmacology as well as drug separation and extraction technology. The project will provide the active material basis and scientific theoretical basis for the research and development of anti-triple negative breast cancer drugs, and also provide novel insights into the innovation and modernization for local characteristic Chinese medicine.