Regulation of tumour immune response by activation of type Ⅰ interferon via TBK1 of cGAS‑STING pathway by Sophorae Flavescentis Radix‑Smilacis Glabrae Rhizoma in non‑small cell lung cancer

WU Yonghui; YU Fengzhi; CAO Yajuan; GU Zhan; FAN Rui; PENG Yanbin; LIANG Zhiwei; SHABATULA Asika; SU Mingliang; YIN Jinjin; WANG Lixin

doi:10.16305/j.1007-1334.2026.z20250510003

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Regulation of tumour immune response by activation of type Ⅰ interferon via TBK1 of cGAS‑STING pathway by Sophorae Flavescentis Radix‑Smilacis Glabrae Rhizoma in non‑small cell lung cancer

更新时间：2026-02-09

- Regulation of tumour immune response by activation of type Ⅰ interferon via TBK1 of cGAS‑STING pathway by Sophorae Flavescentis Radix‑Smilacis Glabrae Rhizoma in non‑small cell lung cancer
- Shanghai Journal of Traditional Chinese Medicine Vol. 60, Issue 2, Pages: 86-93(2026)
- 作者机构：
  
  1.同济大学附属上海市肺科医院中西医结合科（上海 200433）
  2.上海中医药大学研究生院（上海 201203）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2026.z20250510003
  CLC：
- Received：10 May 2025，
  
  Published：10 February 2026
- 稿件说明：
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吴勇汇,于凤至,曹亚娟,等.苦参⁃土茯苓通过cGAS⁃STING通路的TBK1激活Ⅰ型干扰素调节非小细胞肺癌肿瘤免疫应答[J].上海中医药杂志,2026,60(2):86-93.

WU Yonghui,YU Fengzhi,CAO Yajuan,et al.Regulation of tumour immune response by activation of type Ⅰ interferon via TBK1 of cGAS‑STING pathway by Sophorae Flavescentis Radix‑Smilacis Glabrae Rhizoma in non‑small cell lung cancer[J].Shanghai Journal of Traditional Chinese Medicine,2026,60(2):86-93.
吴勇汇,于凤至,曹亚娟,等.苦参⁃土茯苓通过cGAS⁃STING通路的TBK1激活Ⅰ型干扰素调节非小细胞肺癌肿瘤免疫应答[J].上海中医药杂志,2026,60(2):86-93. DOI： 10.16305/j.1007-1334.2026.z20250510003.

WU Yonghui,YU Fengzhi,CAO Yajuan,et al.Regulation of tumour immune response by activation of type Ⅰ interferon via TBK1 of cGAS‑STING pathway by Sophorae Flavescentis Radix‑Smilacis Glabrae Rhizoma in non‑small cell lung cancer[J].Shanghai Journal of Traditional Chinese Medicine,2026,60(2):86-93. DOI： 10.16305/j.1007-1334.2026.z20250510003.

摘要

目的

探究苦参-土茯苓作为一种潜在的固有免疫调节剂在非小细胞肺癌治疗中的作用及分子机制。

方法

采用细胞计数试剂盒（CCK-8）法检测苦参-土茯苓对非小细胞肺癌A549细胞活力的影响。分别使用苦参-土茯苓、干扰素刺激DNA（ISD）、环状GMP-AMP（cGAMP）、脂多糖（LPS）、聚肌苷酸［poly（I：C）］处理C57BL/6小鼠腹腔巨噬细胞，采用实时荧光定量逆转录聚合酶链式反应（RT-qPCR）法检测其Ⅰ型干扰素［CXC趋化因子配体10（

CXCL10

）、β干扰素（

IFN

）、白细胞介素-6（

）］mRNA的表达。使用TANK结合激酶1（TBK1）抑制剂（TBK1-IN-1）和苦参-土茯苓处理A549细胞，分别采用RT-qPCR法和Western blot法检测A549细胞中Ⅰ型干扰素蛋白及其mRNA的表达。使用苦参-土茯苓或苦参-土茯苓+TBK1抑制剂处理A549细胞后，采用Western blot法检测TBK1、磷酸化TBK1（p-TBK1）、干扰素调节因子3（IRF3）、磷酸化IRF3（p-IRF3）蛋白的表达。

结果

CCK-8结果显示苦参-土茯苓能够抑制A549细胞增殖，其半抑制浓度（IC

）为103.2 g/L。在野生型小鼠腹腔巨噬细胞及A549细胞中，苦参-土茯苓各组Ⅰ型干扰素mRNA的表达水平明显高于对照组（

0.05）；ISD、cGAMP能够增强苦参-土茯苓诱导Ⅰ型干扰素mRNA表达的作用（

0.05），而LPS和poly（I：C）对该作用无明显影响（

0.05）。在环鸟腺苷酸合成酶基因（

cGAS

）敲除（

cGAS

-/-

）和干扰素激活蛋白基因（

STING

）敲除（

STING

-/-

）的小鼠腹腔巨噬细胞中，敲除

cGAS

和

STING

并未影响苦参-土茯苓诱导Ⅰ型干扰素表达（

0.05）。在经TBK1抑制剂处理的A549细胞中，苦参-土茯苓组Ⅰ型干扰素的表达

高于对照组及TBK1抑制剂+苦参-土茯苓组，差异有统计学意义（

0.05）。苦参-土茯苓能明显提高TBK1、IRF3蛋白的表达和磷酸化水平（

0.05，

0.01），且该作用能被TBK1抑制剂抑制（

0.01）。

结论

苦参-土茯苓能够抑制非小细胞肺癌细胞增殖，其作用机制可能通过调控cGAS-STING通路的TBK1，从而激活Ⅰ型干扰素反应调控抗肿瘤免疫应答。

Abstract

Objective

To investigate the effect and molecular mechanisms of the Sophorae Flavescentis Radix （Kushen）-Smilacis Glabrae Rhizoma （Tufuling） as a potential innate immune modulator in the treatment of non-small cell lung cancer.

Methods

The Cell Counting Kit （CCK-8） assay was used to evaluate the effect of Kushen-Tufuling on the activity of non-small cell lung cancer A549 cells. C57BL/6 mouse peritoneal macrophages （MPMs） were treated with Kushen-Tufuling， interferon stimulatory DNA （ISD）， cyclic GMP-AMP （cGAMP）， lipopolysaccharide （LPS） or polyinosinic acid ［poly（I：C）］， and the mRNA expression of type Ⅰ interferons （

CXCL10

，

IFN

，

） was detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction （RT-qPCR）. The A549 cells were treated with a TANK-binding kinase 1 （TBK1） inhibitor （TBK1-IN-1） and Kushen-Tufuling， and RT-qPCR and Western blot were used to detect the protein and mRNA expression of type Ⅰ interferons. The A549 cells were treated with Kushen-Tufuling or Kushen-Tufuling+TBK1 inhibitor， and Western blot was used to detect the expression of TBK1， phosphorylated TBK1 （p-TBK1）， interferon regulatory factor 3 （IRF3） and phosphorylated IRF3 （p-IRF3） proteins.

Results

CCK-8 assay results indicated that the Kushen-Tufuling could inhibit A549 cell proliferation， with a half-maximal inhibitory concentration（IC

） value of 103.2 g/L. In both wild-type MPMs and A549 cells， the expressions of type Ⅰ interferons mRNA in each Kushen-Tufu

ling group were significantly higher than in the control group （

0.05）； ISD and cGAMP could enhance the effect of Kushen-Tufuling in inducing the expression of type Ⅰ interferon mRNA （

0.05）， while LPS and poly（I：C） had no significant effect on this effect （

0.05）. In

cGAS

gene knockout （

cGAS

-/-

） and

STING

gene knockout （

STING

-/-

）

MPMs， the knockout of

cGAS

STING

genes did not affect the induction of type Ⅰ interferons expression by Kushen-Tufuling （

0.05）. In the TBK1 inhibitor-treated A549 cells， the expression of type Ⅰ interferons in the Kushen-Tufuling group was significantly higher than in the control and TBK1 inhibitor+Kushen-Tufuling groups （

0.05）.

Conclusion

Kushen-Tufuling can inhibit the proliferation of non-small cell lung cancer cells， potentially by modulating TBK1 in cGAS-STING pathway， thereby activating the type Ⅰ interferons response and regulating anti-tumor immunity.

关键词

Keywords

references

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