| 蔡旻诺,陈卓,张爱琴.清肺合剂抑制非小细胞肺癌犬尿氨酸产生并降低T细胞芳烃受体受体表达的机制研究[J].浙江中西医结合杂志,2026,36(6): |
| 清肺合剂抑制非小细胞肺癌犬尿氨酸产生并降低T细胞芳烃受体受体表达的机制研究 |
| Mechanism of Qingfei Mixture Inhibiting Kynurenine in Non-Small Cell Lung Cancer and Reducing T-Cell AhR Receptor Expression |
| 投稿时间：2025-09-24 修订日期：2026-04-21 |
| DOI： |
| 中文关键词: 非小细胞肺癌 免疫微环境 清肺合剂 色氨酸代谢 |
| 英文关键词:Non-Small Cell Lung Cancer Immune microenvironment Qingfei mixture tryptophan metabolism |
| 基金项目:国家自然科学基金项目（面上项目，重点项目，重大项目）；浙江省自然科学基金项目；国家自然科学基金青年科学基金项目； |
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| 中文摘要: |
| 目的 探究清肺合剂减少非小细胞肺癌（NSCLC）小鼠犬尿氨酸（Kyn）产生降低T细胞芳烃受体（AhR）表达的作用及其机制。方法 在外源性补充色氨酸（Trp）的基础上，用清肺合剂、程序性死亡受体-1（PD-1）抑制剂等干预CD8+T、Lewis肺癌细胞共培养体系，通过细胞计数试剂盒-8（CCK-8）检测细胞活力，酶联免疫吸附试验（ELISA）检测细胞上清中犬尿氨酸的表达情况，蛋白质印迹（WB）检测CD8+T细胞AhR、PD-1蛋白表达。结果 清肺合剂显著抑制NSCLC细胞生长（P<0.05或P<0.01）。与CD8+共培养对照组比较，清肺合剂含药血清组和PD-1抑制剂组细胞上清中犬尿氨酸含量均显著下降[（86.05±8.70）pmol/mL、（113.83±11.64）pmol/mL比（138.07±15.71）pmol/mL，P<0.05或P<0.01]，CD8+T细胞AhR[（0.48±0.05）、（0.59±0.08）比（0.82±0.12），P<0.05或P<0.01]、PD-1蛋白[（0.67±0.06）、（0.51±0.04）比（0.91±0.07），P<0.05或P<0.01]表达水平均显著性降低。与清肺合剂含药血清组和PD-1抑制剂组比较，PD-1抑制剂+清肺合剂含药血清组细胞活力以及细胞上清中犬尿氨酸含量显著下降[（59.11±7.63）pmol/mL比（86.05±8.70）pmol/mL、（113.83±11.64）pmol/mL，P<0.01]，CD8+T细胞AhR[（0.26±0.07）比（0.48±0.05）、（0.59±0.08），P<0.05或P<0.01]、PD-1蛋白[（0.28±0.03）比（0.48±0.05）、（0.59±0.08），P<0.05或P<0.01]表达水平显著性降低。与PD-1抑制剂+清肺合剂含药血清组比较，PD-1抑制剂+清肺合剂含药血清+信号传导及转录激活因子1（STAT1）激动剂组和PD-1抑制剂+清肺合剂含药血清+AhR受体激动剂组细胞上清中犬尿氨酸含量均显著增加[（98.26±11.35）pmol/mL、（92.03±10.16）pmol/mL比（59.11±7.63）pmol/mL，P<0.01]，CD8+T细胞AhR[（0.54±0.07）、（0.48±0.04）比（0.26±0.07），P<0.05或P<0.01]、PD-1蛋白[（0.49±0.12）、（0.62±0.10）比（0.28±0.03），P<0.05或P<0.01]表达水平均显著性升高。结论 清肺合剂能降低CD8+T细胞AhR受体和PD-1的表达水平，其可能是通过抑制NSCLC犬尿氨酸产生实现的，且与PD-1抑制剂合用有协同增效作用。 |
| 英文摘要: |
| Objective Investigation of the effects and mechanisms of Qingfei Mixture in reducing the production of kynurenine (Kyn) in non-small cell lung cancer (NSCLC) mice and decreasing the expression of aryl hydrocarbon receptor (AhR) in T cells. Methods Based on exogenous supplementation of tryptophan (Trp), interventions with Qingfei Mixture, programmed cell death receptor-1 (PD-1) inhibitors, and others were applied to co-culture systems of CD8+T cells and Lewis lung cancer cells. Cell viability was detected by using the cell counting kit-8 (CCK-8) assay, the expression of kynurenine in cell supernatants was measured by enzyme-linked immunosorbent assay (ELISA), and the protein expression of AhR and PD-1 in CD8+T cells was detected by Western blot (WB). Results Qingfei Mixture significantly inhibited the growth of NSCLC cells (P<0.05 or P<0.01). Compared with the CD8+ co-culture control group, the content of kynurenine in the supernatant of the cells in the serum group and the PD-1 inhibitor group was significantly decreased [(86.05±8.70) pmol/mL, (113.83±11.64) pmol/mL vs. (138.07±15.71) pmol/mL, P<0.05 or P<0.01], and the AhR of CD8+T cells [(0.48±0.05), (0.59±0.08) ratio (0.82±0.12), P<0.05 or P <0.01], PD-1 protein [(0.67±0.06), (0.51±0.04) ratio (0.91±0.07), P<0.05 or P<0.01] expression levels were significantly reduced. Compared with the Qingfei Mixture drug-containing serum group and the PD-1 inhibitor group, the cell viability and the content of kynurenine in the cell supernatant were significantly reduced in the PD-1 inhibitor and Qingfei Mixture drug-containing serum group [(59.11±7.63) pmol/mL vs. (86.05±8.70) pmol/mL, (113.83±11.64) pmol/mL, P<0.01], and CD8+T cell AhR [(0.26±0.07) ratio (0.48±0.05), (0.59±0.08), P<0.05 or P <0.01] and PD-1 protein [(0.28±0.03) were significantly lower than those of (0.48±0.05), (0.59±0.08), P<0.05 or P<0.01]. Compared with the PD-1 inhibitor Qingfei Mixture containing the drug-containing serum, the content of kynurenine in the cell supernatant of the PD-1 inhibitor Qingfei Mixture Signaling and Activator 1 (STAT1) agonist group and the PD-1 inhibitor Qingfei Mixture containing the drug-containing serum was significantly increased [(98.26±11.35) pmol/mL, (92.03±10.16) pmol/mL compared with (59.11±7.63) pmol/mL, P <0.01], CD8+T cells had a significant increase in the expression levels of AhR [(0.54±0.07), (0.48±0.04) to (0.26±0.07), P<0.05 or P<0.01], PD-1 protein [(0.49±0.12), (0.62±0.10) to (0.28±0.03), and P<0.05 or P<0.01]. Conclusion The Qingfei Mixture reduces expression levels of the AhR receptor and PD-1 on CD8+T cells, potentially achieved by inhibiting uric acid production in NSCLC. It exhibits synergistic effects when combined with PD-1 inhibitors. |
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