从抑制髓源抑制性细胞的募集探索肺瘤平联合化疗对肺癌的作用和机制  

Effects and Mechanisms of Feiliuping Ointment Combined with Chemotherapyon Lung Cancer through Inhibiting the Recruitment of MDSCs

作　　者：耿良 吕静 范敬 Geng Liang;Lü Jing;Fan Jing(Cancer Hospital Affiliated to Zhengzhou University,Zhengzhou 450008,China;Traditional Chinese Medicine Teaching and Research Office,Zhengzhou Health Vocational College,Zhengzhou 450005,China;College of Management,Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属肿瘤医院,郑州450008 [2]郑州卫生健康职业学院中医教研室,郑州450005 [3]河南中医药大学管理学院,郑州450000

出　　处：《世界科学技术-中医药现代化》2020年第10期3711-3717,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(81473638):从调控炎性微环境抑制肿瘤对骨髓来源细胞的募集和修饰探讨肺瘤平膏对肺癌的作用及机制,负责人:耿良;河南省科学技术厅科技攻关项目(172102310104):扶正解毒法调控肿瘤炎性微环境减少肺癌复发转移的作用及机制研究,负责人:耿良。

摘　　要：目的观察肺瘤平膏和化疗药物对肺癌荷瘤小鼠肿瘤生长的影响,并通过分子生物学方法探索其内在的作用机制。方法通过注射Lewis肺癌细胞悬液建立荷瘤小鼠模型并分为生理盐水、环磷酰胺、肺瘤平、环磷酰胺+肺瘤平4组,分别给与相应干预,记录各组小鼠的瘤块变化、食物消耗量。提取小鼠外周血、脾脏和肿瘤局部的细胞,流式细胞术检测其中Gr-1+CD11b+髓源抑制性细胞(Myeloid-derived suppressor cells,MDSCs)的比例,取肿瘤组织和外周血血清采用Western Blot法和ELISA法检测炎症通路和肿瘤相关细胞因子的表达。结果肺瘤平+环磷酰胺组小鼠的肿瘤体积最小,消耗食物最多,同时该组小鼠外周血、脾脏、肿瘤组织中的MDSCs比例在各组中最低,并伴有TNF-α/IL-1-NF-κB/STAT3炎症通路的抑制和MCP-1、VEGF、MMP-2、MMP-9等炎性因子表达的下调。结论化疗与肺瘤平膏可协同抑制肺癌生长,而这种协同作用部分是因为二者联用可以抑制TNF-α/IL-1-NF-κB/STAT3炎症通路、调控肿瘤局部微环境从而抑制肿瘤对骨髓来源细胞的募集来实现的。Objective To observe the effects of Feiliuping ointment and chemotherapeutics on the growth of tumors in mice with lung cancer, and explore the mechanisms of this treatment by molecular biology methods. Methods The Lewis lung cancer cell suspension was injected to establish a lung cancer mouse model. These mice were divided into 4 groups(saline group, Feiliuping group, cyclophosphamide group, Feiliuping+cyclophosphamide group). Each group received the appropriate intervention. The tumor size and food consumption of the mice in each group were recorded. The peripheral blood, spleen cells, and tumor cells of the mice were collected. Flow cytometry was adopted to detect the ratio of Gr-1+CD11 b+MDSCs, and the expression of inflammation pathway and tumor correlated cytokines were detected by Western Blot and ELISA. Results The smallest size of the tumor and the highest food consumption were observed in the Feiliuping+cyclophosphamide group. At the same time, the proportion of MDSCs in peripheral blood, spleen tissue,and tumor tissue of the mice in this group was the lowest. Besides, the inhibition of TNF-α/IL-1-NF-κB/STAT3 inflammation pathway and decline of tumor correlated cytokines concentration such as MCP-1, VEGF, MMP-2, and MMP-9 were also observed. Conclusion The cooperative effects of Chemotherapeutics+Feiliuping on the inhibition of tumor growth is partly owed to the inhibition of MDSCs recruitment through inhibiting the TNF-α/IL-1-NF-κB/STAT3 inflammation pathway and regulating the tumor microenvironment.

关 键 词：肺癌 炎性微环境 髓源抑制性细胞 肺瘤平膏 化疗 

分 类 号：R273[医药卫生—中西医结合]