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目的 探讨扶金化积丸治疗非小细胞肺癌(NSCLC)的作用机制。方法 56只C57BL/6小鼠随机分为7组,设空白组8只,余48只于腋下接种Lewis细胞,构建肺癌移植瘤模型后,随机分为模型组、扶金化积丸低剂量组、扶金化积丸中剂量组、扶金化积丸高剂量组(0.54、1.07、2.14 g/(kg·d)灌胃)、PD-1抑制剂组(腹腔注射200μg Anti-PD-1)、联合组(予扶金化积丸药液2.14 g/kg灌胃,同时腹腔注射Anti-PD-1),每组8只,每3天测量小鼠体质量及肿瘤体积,干预13 d后处死小鼠,收集胸腺、脾脏,并计算胸腺指数、脾脏指数;绘制体质量、肿瘤体积曲线;收集肿瘤组织,计算抑瘤率;流式细胞术检测肿瘤组织中浸润的CD3+、CD4+、CD8~+T淋巴细胞数量变化;酶联免疫吸附试验检测肿瘤组织中颗粒酶B、穿孔素水平;逆转录实时聚合酶链反应检测肿瘤组织中PD-1、PD-L1、CD8的mRNA及蛋白表达情况。结果 与模型组比较,扶金化积丸高剂量组、PD-1抑制剂组、联合组肿瘤体积缩小、瘤质量降低、CD8蛋白表达水平升高(P<0.05);除扶金化积丸低剂量组,其他干预组胸腺指数、脾脏指数、CD3+、CD8~+T淋巴细胞、颗粒酶B、穿孔素水平均升高,且各干预组CD4~+T淋巴细胞均降低(P<0.05);扶金化积丸各干预组及联合组肿瘤组织中的PD-1、PD-L1 mRNA及蛋白表达水平均降低,CD8 mRNA表达水平均升高(P<0.05)。与PD-1抑制剂组比较,联合组瘤质量、体积及肿瘤组织浸润的CD4~+T淋巴细胞水平、PD-1 mRNA、PD-L1 mRNA、PD-1蛋白、PD-L1蛋白水平均降低,脾脏指数及肿瘤组织浸润的CD3~+T、CD8~+T、颗粒酶B、穿孔素及CD8 mRNA均升高(P<0.05)。金化积丸低、中、高剂量组和PD-1抑制剂组、联合组小鼠肿瘤抑瘤率依次升高(P<0.05),并呈剂量依赖性。结论 扶金化积丸能通过增强Lewis荷瘤小鼠抗肿瘤免疫力及抑制PD-1/PD-L1通路介导的免疫逃逸发挥抗NSCLC的作用,并能增强PD-1抑制剂抗肿瘤能力。
Abstract：Objective To investigate the mechanism of Fujin Huaji pills in the treatment of non-small cell lung cancer(NSCLC). Methods Fifty-six C57BL/6 mice were randomly divided into seven groups: a blank control group(n=8), and the remaining 48 mice received Lewis cell inoculation in the axilla. After establishing a lung cancer xenograft model, the mice were randomly divided into the model group, low-dose Fujin Huaji pills group, medium-dose Fujin Huaji pills group, high-dose Fujin Huaji pills group [0.54, 1.07, 2.14 g/(kg·d) by gavage], PD-1 inhibitor group(intraperitoneal injection of 200 μg Anti-PD-1), and combination group(2.14 g/kg Fujin huaji pill solution by gavage combined with intraperitoneal Anti-PD-1 injection, with 8 mice in each group. Body weight and tumor volume were measured every 3 d. Mice were euthanized at 13 d after intervention. Thymus and spleen were collected to calculate thymus index and spleen index, and body weight and tumor volume curves were drawn. Tumor tissues were collected and tumor suppression rate was calculated. Changes in infiltrating CD3+, CD4+, and CD8+ T cell numbers in tumor tissue were detected by flow cytometry, and granzyme B and perforin levels in tumor tissue were detected using ELISA; mRNA and protein expression of PD-1, PD-L1, and CD8 in tumor tissue were detected by reverse transcription real-time polymerase chain reaction(RT-qPCR). Results Compared with the model group, the high-dose Fujin Huaji pills group, PD-1 inhibitor group, and combination therapy group exhibited reduced tumor volume, decreased tumor weight, and elevated CD8 protein levels(P<0.05). Except the low-dose Fujin Huaji pills group, all intervention groups showed increased thymus index, spleen index, CD3+, CD8+ T cells, granzyme B, and perforin levels, while CD4+ T cells decreased across all intervention groups(P<0.05). mRNA and protein expression levels of PD-1 and PD-L1 were decreased in tumor tissues across all Fujin Huaji intervention groups and the combination group, while CD8 mRNA expression levels were increased(P<0.05). Compared with the PD-1 inhibitor group, the combination group exhibited reduced tumor weight, tumor volume, CD4+ T lymphocyte levels in tumor-infiltrating tissue, PD-1 mRNA, PD-L1 mRNA, PD-1 protein, and PD-L1 protein expression levels(P<0.05), but elevated spleen index, the levels of CD3+ T cells in tumor-infiltrating lymphocytes, CD8+ T cells, granzyme B, perforin, and CD8 mRNA(P<0.05). Tumor inhibition rates in mice treated with low, medium, and high doses of Fujin Huaji pills, the PD-1 inhibitor and combination groups, increased in ascending order and in a dose-dependent manner. Conclusion Fujin Huaji pills exert anti-NSCLC effects by enhancing anti-tumor immunity and inhibiting PD-1/PD-L1 pathway-mediated immune escape in Lewis tumor-bearing mice, while also potentiating the anti-tumor efficacy of PD-1 inhibitors.
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基本信息:
DOI：10.13431/j.cnki.immunol.j.20260025
中图分类号:R285.5
引用信息:
[1]任德祥,刘榕,吕学颖,等.扶金化积丸治疗非小细胞肺癌的机制研究[J].免疫学杂志,2026,42(03):166-174.DOI:10.13431/j.cnki.immunol.j.20260025.
基金信息:
国家自然科学基金项目(82174463); 甘肃省科技厅重点研发计划项目(24YFFA019); 甘肃省自然科学基金项目(23JRRA1252); 甘肃省中医药人才培养重点学科建设项目([甘财社(2022)48号]); 甘肃省名中医传承工作室建设项目([国中医药规财函(2021)242]); 兰州市人才创新创业项目(2017-RC-45); 2026年度甘肃中医药大学研究生创新创业基金项目(2026CXCY-029)
2026-03-28
2026-03-28