芪玉三龙汤通过PD-1信号通路增强Th1免疫反应抑制肺癌转移  

Qiyu Sanlong Decoction enhances Th1 immune response through PD-1 signaling pathway and inhibits metastasis of lung cancer

作　　者：焦安男 吴欢 朱洁[3] 张梅[1] 李平[1] 李泽庚[4] 陈杨 Jiao Annan;Wu Huan;Zhu Jie;Zhang Mei;Li Ping;Li Zegeng;Chen Yang(Dept of Integrated Traditional Chinese and Western Medicine Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Scientific Research&Experiment Center,Anhui University of Chinese Medicine,Hefei 230038;Dept of Integrated Traditional Chinese and Western Medicine Oncology,Anhui University of Chinese Medicine,Hefei 230038;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230601)

机构地区：[1]安徽医科大学第一附属医院中西医结合肿瘤科,合肥230022 [2]安徽中医药大学科研实验中心,合肥230038 [3]安徽中医药大学中西医结合学院,合肥230038 [4]安徽中医药大学第一附属医院,合肥230601

出　　处：《安徽医科大学学报》2022年第11期1718-1724,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学青年基金(编号:82004314);安徽医科大学第一附属医院临床研究启动计划(编号:LCYJ2021YB017);CSCO-罗氏实体肿瘤研究基金(编号:Y-Roche2019/2-0079);中华国际医学交流基金会中青年医学研究专项基金(编号:Z-2014-06-2102);安徽医科大学第一附属医院青年培养计划(编号:2018kj31)。

摘　　要：目的探讨芪玉三龙汤(QYSLD)通过PD-1信号通路调节肿瘤免疫微环境抑制肺癌及对肺癌荷瘤小鼠Th1免疫反应的影响。方法应用Lewis肺癌细胞株(LLC)细胞培养移植法建立小鼠皮下移植瘤模型,将72只模型小鼠随机分为对照组、顺铂组、QYSLD组和联合组,每组18只。观察小鼠一般生存情况;应用ELISA法检测小鼠肿瘤抗原特异性Th1细胞反应情况;流式细胞术检测小鼠脾脏T细胞中PD-1阳性细胞比例及记忆性CD4^(+)T细胞凋亡情况;药物处理小鼠21 d后,在解剖显微镜下计数肺表面转移瘤结节的数目与体积。结果QYSLD可改善肺癌荷瘤小鼠一般生存情况,上调小鼠CD4^(+)T细胞免疫反应及CD8^(+)T细胞特异性杀肿瘤细胞效应,下调小鼠脾脏T细胞中PD-1阳性细胞及CD4^(+)记忆性T细胞中凋亡细胞的比例;抑制小鼠肿瘤细胞的肺转移。结论QYSLD可改善肺癌荷瘤小鼠的生存状态并通过介导PD-1信号通路,增强Th1免疫反应,调节肿瘤免疫微环境,抑制肿瘤细胞免疫逃逸,从而达到抑制肺癌转移的作用。Objective To investigate the effect of Qiyu Sanlong Decoction(QYSLD)on inhibiting lung cancer by regulating tumor immune microenvironment through PD-1 signaling pathway and on Th1 immune response in lung cancer bearing mice.Methods Lewis lung cancer cell line(LLC)was used to model subcutaneously implanted tumor in mice.72 mice were randomly divided into Control group(n=18),cisplatin group(n=18),QYSLD group(n=18)and combined group(n=18).The general survival of mice was observedand recorded;the specific Th1 cell response to tumor antigen was detected by ELISA method;the proportion of PD-1 positive cells and the apoptosis of memory CD4^(+)T cells in spleen T cells of mice were detected by flow cytometry;and the number and volume of pulmonary metastatic nodules were counted under an anatomical microscope after 21 days of continuous treatment.Results QYSLD could improve the general survival of mice bearing lung cancer,up-regulate the immune response of CD4^(+)T cells and the specific killing effect of CD8^(+)T cells.The proportion of apoptotic cells in PD-1 positive cells and CD4^(+)memory T cells in spleen T cells of mice was down-regulated,and lung metastasis of mouse tumor cells was inhibited.Conclusion QYSLD can improve the survival status of mice bearing lung cancer and enhance Th1 immune response by mediating PD-1 signaling pathway,improve immune function and inhibit immune escape of tumor cells,thus inhibiting the metastasis of lung cancer.

关 键 词：肺癌 芪玉三龙汤 PD-1 TH1 转移 

分 类 号：R285.5[医药卫生—中药学]