壮药扶正方通过改善Lewis肺癌CD8+ T细胞耗竭提高PD-L1抑制剂疗效的机制研究

doi:10.13418/j.issn.1001-165x.2025.1.10

PDF(3652 KB)

中国临床解剖学杂志 ›› 2025, Vol. 43 ›› Issue (1) : 63-68. DOI: 10.13418/j.issn.1001-165x.2025.1.10

实验研究

壮药扶正方通过改善Lewis肺癌CD8⁺ T细胞耗竭提高PD-L1抑制剂疗效的机制研究

莫娟梅¹，张顺荣¹，李健²，王振宁¹，唐伟智¹，梁碧琦¹，庞宇舟²，
周建龙¹，周韶璋³ ，黄国东¹*

作者信息 +

The mechanism of Zhuang Medicine Fuzheng Compound improving the efficacy of PD-L1 inhibitor by improving CD8⁺T cell depletion in Lewis lung cancer

Mo Juanmei¹, Zhang Shunrong¹, Li Jian ², Wang Zhenning¹, Tang Weizhi², Liang Biqi¹, Pang Yuzhou², Zhou Jianlong¹, Zhou Shaozhang³, Huang Guodong¹*

Author information +

文章历史 +

摘要

目的探讨壮药扶正方对小鼠肺癌浸润的CD8+ T细胞耗竭以及对PD-L1抑制剂疗效的影响，并明确其中可能的机制。方法 MTT、平板克隆检测壮药扶正方对小鼠肺癌LLC细胞增殖能力影响；流式细胞术检测CD8+ T的比例以及检测PD-L1表达水平，并利用Western blot检测蛋白水平表达初步探讨相关机制；最后通过动物体内实验验证壮药扶正方和PD-L1抑制剂协同作用。结果壮药扶正方可抑制小鼠肺癌LLC细胞增殖能力；在小鼠体内实验中，壮药扶正方和PD-L1抑制剂可起到协同抗肿瘤作用；壮药扶正方延缓CD8+ T细胞的耗竭情况，并抑制PD-L1表达；壮药扶正方可降低PI3K/AKT通路活性。结论壮药扶正方可延缓CD8+ T细胞耗竭和抑制PD-L1表达，增强PD-L1抑制剂治疗肺癌的疗效，机制可能与降低PI3K/AKT信号通路有关。

Abstract

Objective To investigate the effect of Zhuang Medicine Fuzheng Compound on the exhaustion of CD8+ T cells infiltrated by lung cancer and the efficacy of PD-L1 inhibitors, and to clarify the possible mechanism. Methods MTT and plate cloning were used to detect the effect of Zhuang Medicine Fuzheng Compound on the proliferation of LLC cells of mouse lung cancer. Flow cytometry was used to detect the proportion of CD8+T and the expression level of PD-L1, and Western blot was used to detect the expression level of protein to preliminarily explore the relevant mechanism. Finally, the synergistic effect of Zhuang Medicine Fuzheng Compound and PD-L1 inhibitor was verified by animal experiments. Results Zhuang Medicine Fuzheng Compound inhibited the proliferation of LLC cells in mice. In vivo experiments in mice, Zhuang Medicine Fuzheng Compound and PD-L1 inhibitor could play a synergistic anti-tumor effect. Zhuang Medicine Fuzheng Compound delayed the depletion of CD8+ T cells and inhibited the expression of PD-L1. Zhuang Medicine Fuzheng Compound could reduce the activity of PI3K/AKT pathway. Conclusions Zhuang Medicine Fuzheng Compound can delay CD8+ T cell depletion and inhibit PD-L1 expression, and enhance the efficacy of PD-L1 inhibitors in the treatment of lung cancer, which may be related to the reduction of PI3K/AKT signaling pathway.

导出引用

莫娟梅, 张顺荣, 李健, 王振宁, 唐伟智, 梁碧琦, 庞宇舟, 周建龙, 周韶璋, 黄国东. 壮药扶正方通过改善Lewis肺癌CD8⁺ T细胞耗竭提高PD-L1抑制剂疗效的机制研究[J]. 中国临床解剖学杂志. 2025, 43(1): 63-68 https://doi.org/10.13418/j.issn.1001-165x.2025.1.10

Mo Juanmei, Zhang Shunrong, Li Jian, Wang Zhenning, Tang Weizhi, Liang Biqi, Pang Yuzhou, Zhou Jianlong, Zhou Shaozhang, Huang Guodong. The mechanism of Zhuang Medicine Fuzheng Compound improving the efficacy of PD-L1 inhibitor by improving CD8⁺T cell depletion in Lewis lung cancer[J]. Chinese Journal of Clinical Anatomy. 2025, 43(1): 63-68 https://doi.org/10.13418/j.issn.1001-165x.2025.1.10

中图分类号： R736.1

参考文献

[1] Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl),2022,135(5): 584-590. DOI: 10.1097/CM9.0000000000002108.
[2] 魏文海, 李兴芳, 赵琼, 等. PI3K/Akt/mTOR信号通路抗非小细胞肺癌的机制及中药干预研究进展[J]. 中国实验方剂学杂志, 2023, 29(23): 218-226. DOI: 10.13422/j.cnki.syfjx.20230221.
[3] Miller BC, Sen DR, Abosy Al R, et al. Subsets of Exhausted CD8+ T Cells Differentially Mediate Tumor Control and Respond to Checkpoint Blockade[J]. Nat Immunol, 2019, 20:326-36. DOI: 10.1038/s41590-019-0312-6.
[4] 闵翼, 张曦尧, 向东阳, 等. 芡茎多糖通过诱导CD4+ T、CD8+ T和NK细胞的浸润促进小鼠肺癌LLC细胞凋亡[J]. 南京中医药大学学报, 2023, 39(7):637-644. DOI: 10.14148/j.issn.1672-0482.2023.0637.
[5] 兰煜, 范国栋, 王婷, 等. 芪玉三龙汤调节小鼠腹腔巨噬细胞M2/M1型极化及其对CD4+、CD8+T细胞的影响[J]. 安徽中医药大学学报, 2023, 42(4):88-92. DOI: 10.3969/j.issn.2095-7246.2023.04.019.
[6] 莫娟梅, 张顺荣, 梁潇, 等. 壮药扶正复方辅助治疗晚期表皮生长因子受体敏感型突变非小细胞肺癌临床研究[J]. 国际中医中药杂志, 2022, 44(10):1102-1106. DOI:10.3760/cma.j.cn115398-20211222-00233.
[7] 陈康, 金晨, 程玉瑶, 等. 基于网络药理学和分子对接探讨鸡血藤治疗肺癌的分子作用机制[J]. 中国中药杂志, 2021, 46(4):837-844. DOI: 10.19540/j.cnki.cjcmm.20201118.401.
[8] Zheng J, Wu M, Wang H, et al. Network pharmacology to unveil the biological basis of health-strengthening herbal Medicine in cancer treatment[J]. Cancers (Basel), 2018, 10(11):461. DOI: 10.3390/cancers 10110461.
[9] 莫娟梅, 甘芷川, 张顺荣, 等. 扶正方对Lewis肺癌小鼠免疫功能、PI3K/AKT信号通路和外周血IL-2、IL-6、INF-γ的影响[J]. 现代生物医学进展, 2021, 21(23):4422-4426. DOI: 10.13241/j.cnki.pmb. 2021. 23.005.
[10] 张志超, 刘江红, 潘远安. 五指毛桃与黄芪提取物对免疫抑制小鼠细胞免疫的影响[J].中国民族民间医药, 2017, 26(5):58-59. DOI: 10.3969/j.issn.1007-8517.2017.5.zgmzmjyyzz201705018.
[11]张嫦丽, 张可锋, 许有瑞, 等. 黄花倒水莲的化学成分与药理活性研究进展[J]. 中国药房, 2017, 28(19):2724-2728. DOI: 10.6039/j.issn.1001-0408.2017.19.35.
[12]毛跃程, 邢代君, 刘心宁, 等. 汉黄芩素对气虚模型LLC种植瘤小鼠的抗肿瘤作用及淋巴细胞亚群的影响[J]. 中医药导报, 2023, 29(6):1-9. DOI: 10.13862/j.cn43-1446/r.2023.06.001.
[13]Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting[J]. Nat Rev Cancer, 2015,15:7-24. DOI: 10.1038/nrc3860.
[14]Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations[J]. Nat Rev Cancer. 2009, 9:550-562. DOI: 10.1038/nrc2664.