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1.中国人民解放军医学院,北京市海淀区复兴路28号,100853
2.中国人民解放军总医院第六医学中心
3.中国人民解放军71901部队
4.中国人民解放军军事科学院军事医学研究院
Received:26 October 2025,
Revised:2025-12-22,
Published:02 February 2026
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于泓洋,窦永起,邹涛等.黄芪-莪术药对对Lewis肺癌模型小鼠肿瘤组织CD8+T细胞功能及IL-6/JAK2/STAT3/PD-L1通路的影响[J].中医杂志,2026,67(03):314-322. DOI: 10.13288/j.11-2166/r.2026.03.013.
YU Hongyang,DOU Yongqi,ZOU Tao,et al.Effects of Huangqi (Astragalus Mongholicus)-Ezhu(Curcuma Aromatica) Herb Pair on CD8+ T Cell Function and IL-6/JAK2/STAT3/PD-L1 Pathway in Tumor Tissues of Lewis Lung Cancer Model Mice[J].Journal of Traditional Chinese Medicine,2026,67(03):314-322. DOI: 10.13288/j.11-2166/r.2026.03.013.
于泓洋,窦永起,邹涛等.黄芪-莪术药对对Lewis肺癌模型小鼠肿瘤组织CD8+T细胞功能及IL-6/JAK2/STAT3/PD-L1通路的影响[J].中医杂志,2026,67(03):314-322. DOI: 10.13288/j.11-2166/r.2026.03.013. DOI:
YU Hongyang,DOU Yongqi,ZOU Tao,et al.Effects of Huangqi (Astragalus Mongholicus)-Ezhu(Curcuma Aromatica) Herb Pair on CD8+ T Cell Function and IL-6/JAK2/STAT3/PD-L1 Pathway in Tumor Tissues of Lewis Lung Cancer Model Mice[J].Journal of Traditional Chinese Medicine,2026,67(03):314-322. DOI: 10.13288/j.11-2166/r.2026.03.013. DOI:
目的
2
从CD8
+
T细胞抗肿瘤免疫功能及IL-6/JAK2/STAT3/PD-L1通路角度探讨黄芪-莪术抑制Lewis肺癌小鼠肿瘤生长的可能作用机制。
方法
2
40只C57BL/6小鼠腋窝皮下接种Lewis细胞建立肺癌小鼠模型,造模成功后随机分为模型对照组、黄芪-莪术组、程序性死亡配体1(PD-L1)抗体组和联合组,每组10只。于造模第3天开始给药,其中黄芪-莪术组予黄芪-莪术溶液灌胃5.2 g/(kg·d),每日1次,并予每只小鼠腹腔注射生理盐水0.1 ml,每3日1次;PD-L1抗体组予10 ml/(kg·d)蒸馏水灌胃,每日1次,腹腔注射PD-L1抗体10 mg/kg,每3日1次;联合组予黄芪-莪术溶液灌胃及腹腔注射PD-L1抗体,剂量和方式同上;模型对照组予蒸馏水灌胃及腹腔注射生理盐水,剂量和方式同上。各组均给药15天。每3日测量肿瘤体积,末次给药后测量肿瘤质量并计算抑瘤率、胸腺指数及脾脏指数;HE染色观察肿瘤组织病理学变化,流式细胞术检测肿瘤组织中CD8
+
T细胞表型,Western Blot法检测肿瘤组织中白细胞介素6(IL-6)、Janus激酶2(JAK2)、磷酸化Janus激酶2(p-JAK2)、信号转导与转录激活因子3(STAT3)、磷酸化信号转导与转录激活因子3(p-STAT3)、PD-L1蛋白表达,ELISA法检测肿瘤组织中白细胞介素10(IL-10)、干扰素γ(IFN-γ)和IL-6水平。
结果
2
与模型对照组比较,各用药组胸腺指数、脾脏指数、CD8
+
T细胞、CD8
+
IFN-γ
+
T细胞、CD8
+
Gzm B
+
T细胞占比及IFN-γ升高(
P
<0.05),肿瘤体积、肿瘤质量与IL-10降低(
P
<0.01),其中PD-L1抗体组IL-6、p-STAT3表达升高(
P
<0.01),黄芪-莪术与联合组的CD8
+
TIM3
+
T细胞占比、IL-6水平、p-STAT3及PD-L1表达降低(
P
<0.05);与PD-L1抗体组比较,黄芪-莪术组肿瘤体积、肿瘤质量、IL-10升高(
P
<0.05),脾脏指数、CD8
+
T细胞占比、CD8
+
TIM3
+
T细胞占比及p-JAK2降低(
P
<0.05),联合组的CD8
+
Gzm B
+
T细胞升高(
P
<0.05)、IL-10降低(
P
<0.05),且两组的IL-6、p-STAT3表达降低(
P
<0.01);与黄芪-莪术组比较,联合组CD8
+
T细胞占比、p-JAK2、p-STAT3表达升高(
P
<0.01),肿瘤体积、肿瘤质量与IL-10降低(
P
<0.01)。各组JAK2、STAT3总蛋白水平差异无统计学意义(
P
>0.05)。
结论
2
黄芪-莪术能够有效抑制Lewis肺癌荷瘤生长,促进CD8
+
T细胞分化与细胞毒性作用并改善其功能耗竭,改变
肿瘤免疫抑制微环境,且黄芪-莪术与PD-L1抗体联用可进一步提高抑瘤率并改善免疫效应,其作用机制可能与抑制肿瘤组织IL-6/JAK2/STAT3/PD-L1通路相关。
Objective
2
To explore the potential mechanism by which Huangqi (
Astragalus mongholicus
)-Ezhu (
Curcuma aromatica
) herb pair inhibits tumor growth in Lewis lung cancer model mice from the perspectives of CD8
+
T cell anti-tumor immune function and the IL-6/JAK2/STAT3/PD-L1 signaling pathway.
Methods
2
Forty C57BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma cells in the axilla to establish mouse models of lung cancer. After successful modeling, the mice were randomly assigned into four groups (n=10 per group), model control group, Huangqi (
Astragalus mongholicus
)-Ezhu (
Curcuma aromatica
) herb pair group, programmed death-ligand 1 (PD-L1) antibody group, and combination group of herb pair plus PD-L1 antibody. Administration was initiated on the 3rd day after modeling. The herb pair group was given Huangqi (
Astragalus mongholicus
)-Ezhu (
Curcuma aromatica
) solution by gavage at a dose of 5.2 g/(kg·d) once daily, plus intraperitoneal injection of 0.1 ml normal saline per mouse once every 3 days. The PD-L1 antibody group received distilled water by gavage at 10 ml/(kg·d) once daily, plus intraperitoneal injection of PD-L1 antibody at 10 mg/kg once every 3 days. The combination group was treated with Huangqi (
Astragalus mongholicus
)-Ezhu (
Curcuma aromatica
) solution by gavage combined with intraperitoneal injection of PD-L1 antibody at the same doses and administration schedules as described above. The model control group was given distilled water by gavage and intraperitoneal injection of normal saline at the corresponding doses and schedules. The treatment course lasted for 15 days in all groups. Tumor volume was measured every 3 days. After the fina
l administration, tumor weight was recorded to calculate the tumor inhibition rate, thymus index, and spleen index; hematoxylin-eosin (HE) staining was performed to observe the pathological changes of tumor tissues; flow cytometry was used to detect the phenotype of CD8
+
T cells in tumor tissues; Western Blot was employed to determine the protein expressions of interleukin-6 (IL-6), Janus kinase 2 (JAK2), phosphorylated Janus kinase 2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), and PD-L1 in tumor tissues; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-10 (IL-10), interferon-γ (IFN-γ), and IL-6 in tumor tissues.
Results
2
Compared with the model control group, the thymus index, spleen index, proportions of CD8⁺ T cells, CD8⁺ IFN-γ⁺ T cells, and CD8⁺ Gzm B⁺ T cells, as well as IFN-γ levels all increased in the treatment groups (
P
<0.05), while tumor volume, tumor weight, and IL-10 levels decreased (
P
<0.01). IL-6 and p-STAT3 levels elevated in the PD-L1 antibody group (
P
<0.01), whereas the proportions of CD8⁺ TIM3⁺ T cells and the expression levels of IL-6, p-STAT3, and PD-L1 were reduced in the herb pair group and combination groups (
P
<0.05). Compared with the PD-L1 antibody group, the herb pair group showed higher tumor volume, tumor weight, and IL-10 levels (
P
<0.05), and lower spleen index, proportions of CD8⁺ T cells and CD8⁺ TIM3⁺ T cells, as well as reduced p-JAK2 expression (
P
<0.05); in the combination group, the proportion of CD8⁺ Gzm B⁺ T cells increased (
P
<0.05), and IL-10 levels decreased (
P
<0.05); both the herb pair group and combination group exhibited lower IL-6 and p-STAT3 expression compared with the PD-L1 antibody group (
P
<0.01). Compared with the herb pair group, the co
mbination group showed higher proportions of CD8⁺ T cells, as well as elevated p-JAK2 and p-STAT3 expression (
P
<0.01), while tumor volume, tumor weight, and IL-10 levels reduced (
P
<0.01). There was no significant difference in total JAK2 or STAT3 protein expression among the groups (
P
>0.05).
Conclusion
2
The herb pair Huangqi (
Astragalus mongholicus
)-Ezhu (
Curcuma aromatica
) can effectively inhibit tumor growth in Lewis lung cancer model mice, promote the differentiation and cytotoxicity of CD8
+
T cells, improve their functional exhaustion, and remodel the tumor immunosuppressive microenvironment. Furthermore, the combination of Huangqi-Ezhu herb pair with PD-L1 antibody can further enhance the tumor inhibition rate and improve immune efficacy. Its mechanism may be related to the inhibition of the IL-6/JAK2/STAT3/PD-L1 signaling pathway in tumor tissues.
CHEN Y , YU D , QIAN H , et al . CD8(+) T cell-based cancer immunotherapy [J]. J Transl Med , 2024 , 22 ( 1 ): 394 .
YI M , ZHENG X , NIU M , et al . Combination strategies with PD-1/PD-L1 blockade: current advances and future directions [J]. Mol Cancer , 2022 , 21 ( 1 ): 28 .
OLIVEIRA C , MAINOLI B , DUARTE GS , et al . Immune-related serious adverse events with immune checkpoint inhibitors: systematic review and network meta-analysis [J]. Eur J Clin Pharmacol , 2024 , 80 ( 5 ): 677 - 684 .
HUANG B , LANG X , LI X . The role of IL-6/JAK2/STAT3 signaling pathway in cancers [J]. Front Oncol , 2022 , 12 : 1023177 . doi: 10.3389/fonc.2022.1023177 http://dx.doi.org/10.3389/fonc.2022.1023177 .
JEONG H , KOH J , KIM S , et al . Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6/Jak/Stat3 in PD-L1-high lung cancer [J]. J Immunother Cancer , 2025 , 13 ( 3 ): e010612 .
PENG D , YANG W , TANG T , et al . PLA2G7 promotes immune evasion of bladder cancer through the JAK-STAT-PDL1 axis [J]. Cell Death Dis , 2025 , 16 ( 1 ): 234 .
康涵钰 , 李闪闪 , 魏丹丹 , 等 . 黄芪-莪术药对抗肿瘤配伍效应及作用机制研究进展 [J]. 中国实验方剂学杂志 , 2025 , 31 ( 20 ): 276 - 286 .
尹刚 , 唐德才 . 浅议黄芪、莪术在治疗妇科肿瘤中的配伍意义 [J]. 辽宁中医杂志 , 2014 , 41 ( 7 ): 1376 - 1377 .
李潇 , 于泓洋 , 田培裕 , 等 . 黄芪-莪术对Lewis肺癌小鼠肿瘤血管及肿瘤微环境中CD8 + T细胞的影响 [J]. 世界中西医结合杂志 , 2023 , 18 ( 5 ): 929 - 938 .
田培裕 , 于泓洋 , 李潇 , 等 . 黄芪-莪术对C5a介导JAK2/STAT3通路调控Lewis肺癌小鼠Th17/Treg细胞平衡影响的实验研究 [J]. 世界中西医结合杂志 , 2024 , 19 ( 3 ): 425 - 432 .
XIA J , DAI L , WANG L , et al . Ganoderic acid DM induces autophagic apoptosis in non-small cell lung cancer cells by inhibiting the PI3K/Akt/mTOR activity [J]. Chem Biol Interact , 2020 , 316 : 108932 . doi: 10.1016/j.cbi.2019.108932 http://dx.doi.org/10.1016/j.cbi.2019.108932 .
魏伟 , 吴希美 , 李元建 . 药理实验方法学 [M]. 北京 : 人民卫生出版社 , 2010 : 20 - 50 .
梁立 , 齐卓操 , 杨心玥 , 等 . 黄芪莪术联合5-氟尿嘧啶对CT26.WT原位移植瘤小鼠CXCL10/CXCR3轴和CCL3/CCR5轴表达的影响 [J]. 北京中医药大学学报 , 2022 , 45 ( 1 ): 62 - 72 .
骆文龙 , 尹怡 , 王俊涛 , 等 . 理肺散结消岩方对Lewis肺癌小鼠炎性反应和NF-κB信号通路的影响 [J/OL]. 辽宁中医杂志 .( 2025-03-18 )[ 2025-12-31 ]. https://link.cnki.net/urlid/21.1128.r.20250317.1556.006 https://link.cnki.net/urlid/21.1128.r.20250317.1556.006 .
XIA A , ZHANG Y , XU J , et al . T cell dysfunction in cancer immunity and immunotherapy [J]. Front Immunol , 2019 , 10 : 1719 . doi: 10.3389/fimmu.2019.01719 http://dx.doi.org/10.3389/fimmu.2019.01719 .
PARK J , HSUEH PC , LI Z , et al . Microenvironment-driven metabolic adaptations guiding CD8(+) T cell anti-tumor immunity [J]. Immunity , 2023 , 56 ( 1 ): 32 - 42 .
LIN X , KANG K , CHEN P , et al . Regulatory mechanisms of PD-1/PD-L1 in cancers [J]. Mol Cancer , 2024 , 23 ( 1 ): 108 .
YOON HH , JIN Z , KOUR O , et al . Association of PD-L1 expression and other variables with benefit from immune checkpoint inhibition in advanced gastroesophageal cancer: systematic review and Meta-analysis of 17 phase 3 randomized clinical trials [J]. JAMA Oncol , 2022 , 8 ( 10 ): 1456 - 1465 .
ZHANG Z , TANG Y , WANG Y , et al . SIN3B loss heats up cold tumor microenvironment to boost immunotherapy in pancreatic cancer [J]. Adv Sci (Weinh) , 2024 , 11 ( 43 ): e2402244 .
KIM Y , YANG H , LEE WS , et al . High levels of baseline serum IL-10 are associated with reduced clinical benefit from first-line immune checkpoint inhibitor therapy in advanced renal cell carcinoma [J]. J Cancer , 2023 , 14 ( 6 ): 935 - 942 .
周银杰 , 万籽晗 , 余沛霜 , 等 . 黄芪-莪术药对抗肺癌的物质基础及作用机制研究进展 [J]. 中草药 , 2024 , 55 ( 21 ): 7547 - 7556 .
张锡纯 . 医学衷中参西录 [M]. 北京 : 中医古籍出版社 , 2016 : 20 .
于泓洋 , 李潇 , 田培裕 , 等 . 黄芪-莪术对Lewis肺癌小鼠NF-κB通路及肿瘤自噬的干预作用研究 [J]. 世界中西医结合杂志 , 2024 , 19 ( 1 ): 90 - 96 .
杨倩宇 , 闫梓乔 , 李潇 , 等 . 黄芪-莪术抑制肺癌血管生成及其对EGFR/PI3K/AKT和HIF-1α/VEGF信号通路的影响 [J]. 中华中医药杂志 , 2022 , 37 ( 7 ): 4039 - 4043 .
SUN L , SU Y , JIAO A , et al . T cells in health and disease [J]. Signal Transduct Target Ther , 2023 , 8 ( 1 ): 235 .
WOZNICKI JA , SAINI N , FLOOD P , et al . TNF-alpha synergises with IFN-gamma to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells [J]. Cell Death Dis , 2021 , 12 ( 10 ): 864 .
REN J , LI N , PEI S , et al . Histone methyltransferase WHSC1 loss dampens MHC-Ⅰ antigen presentation pathway to impair IFN-gamma-stimulated antitumor immunity [J]. J Clin Invest , 2022 , 132 ( 8 ): e153167 .
LIN Y , SONG Y , ZHANG Y , et al . New insights on anti-tumor immunity of CD8(+) T cells: cancer stem cells, tumor immune microenvironment and immunotherapy [J]. J Transl Med , 2025 , 23 ( 1 ): 341 .
GUÉGAN JP , PEYRAUD F , DADONE-MONTAUDIE B , et al . Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response [J]. Cell Rep Med , 2024 , 5 ( 12 ): 101831 .
BATCHU RB , GRUZDYN OV , KOLLI BK , et al . IL-10 signaling in the tumor microenvironment of ovarian cancer [J]. Adv Exp Med Biol , 2021 , 1290 : 51 - 65 . doi: 10. 1007/978-3-030-55617-4_3 http://dx.doi.org/10.1007/978-3-030-55617-4_3 .
THUYA WL , CAO Y , HO PC , et al . Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: implications for cancer therapy [J]. Cytokine Growth Factor Rev , 2025 , 85 : 26 - 42 . doi: 10.1016/j.cytogfr. 2025.01.003 http://dx.doi.org/10.1016/j.cytogfr.2025.01.003 .
LU Y , XIN D , GUAN L , et al . Metformin downregulates PD-L1 expression in esophageal squamous cell catrcinoma by inhibiting IL-6 signaling pathway [J]. Front Oncol , 2021 , 11 : 762523 . doi: 10.3389/fonc.2021.762523 http://dx.doi.org/10.3389/fonc.2021.762523 .
WEN Z , SUN H , ZHANG Z , et al . High baseline tumor burden-associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2-STAT3-PD-L1 pathway [J]. Cancer Commun (Lond) , 2023 , 43 ( 5 ): 562 - 581 .
刘宏伟 , 陈瑞琦 , 熊洪 , 等 . 黄芪多糖通过调控JAK2/STAT3信号通路抑制膀胱癌UM-UC-3细胞增殖、迁移与侵袭 [J]. 山西医科大学学报 , 2023 , 54 ( 11 ): 1442 - 1448 .
张琰 , 马娜 , 王芳 , 等 . 莪术醇抑制JAK1/STAT3信号通路对肺癌细胞增殖、凋亡和侵袭的影响 [J]. 临床医学研究与实践 , 2021 , 6 ( 34 ): 10 - 15 .
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