Effects of naringin on the proliferation， apoptosis and immune escape of breast cancer cells through cGAS-STING signaling pathway

BAI Wenhui; LI Ying; LI Zonglong

doi:10.6039/j.issn.1001-0408.2025.16.10

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Effects of naringin on the proliferation， apoptosis and immune escape of breast cancer cells through cGAS-STING signaling pathway

更新时间：2025-09-25

- Effects of naringin on the proliferation， apoptosis and immune escape of breast cancer cells through cGAS-STING signaling pathway
- ZHONGGUO YAOFANG Vol. 36, Issue 16, Pages: 2012-2016(2025)
- 作者机构：
  
  青海红十字医院乳腺外科，西宁　810000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.16.10
  CLC： R965
- Received：06 May 2025，
  
  Revised：2025-07-28，
  
  Accepted：29 July 2025，
  
  Published：30 August 2025
- 稿件说明：
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白文辉,李英,李宗龙.柚皮苷通过cGAS-STING信号通路对乳腺癌细胞增殖、凋亡和免疫逃逸的影响[J].中国药房,2025,36(16):2012-2016.

BAI Wenhui,LI Ying,LI Zonglong.Effects of naringin on the proliferation， apoptosis and immune escape of breast cancer cells through cGAS-STING signaling pathway[J].ZHONGGUO YAOFANG,2025,36(16):2012-2016.
白文辉,李英,李宗龙.柚皮苷通过cGAS-STING信号通路对乳腺癌细胞增殖、凋亡和免疫逃逸的影响[J].中国药房,2025,36(16):2012-2016. DOI： 10.6039/j.issn.1001-0408.2025.16.10.

BAI Wenhui,LI Ying,LI Zonglong.Effects of naringin on the proliferation， apoptosis and immune escape of breast cancer cells through cGAS-STING signaling pathway[J].ZHONGGUO YAOFANG,2025,36(16):2012-2016. DOI： 10.6039/j.issn.1001-0408.2025.16.10.

摘要

目的

探讨柚皮苷通过环鸟苷酸-腺苷酸合酶（cGAS）-干扰素基因刺激因子（STING）信号通路对乳腺癌细胞增殖、凋亡和免疫逃逸的影响。

方法

将人乳腺癌细胞系MDA-MB-231分为空白组，柚皮苷低、中、高剂量组（50、100、200 μmol/L），RU.521组（cGAS抑制剂，1 μmol/L）、柚皮苷高剂量+RU.521组（200 μmol/L柚皮苷+1 μmol/L RU.521），各组细胞用相应药液分别处理48 h后，检测MDA-MB-231细胞的增殖[以5-乙炔基-2′-脱氧尿嘧啶核苷（EdU）阳性率和光密度（OD

450

）值计

]

、凋亡情况，以及细胞中增殖细胞核抗原（PCNA）、p53、B7同源物1（B7H1）、程序性死亡受体1（PD-1）、cGAS、STING蛋白表达水平。除空白组外，将上述各组MDA-MB-231细胞分别经相应药物处理48 h后，再与NK细胞共孵育48 h，检测共孵育体系上清液中颗粒酶B、肿瘤坏死因子α（TNF-α）、γ干扰素（IFN-γ）水平以及NK细胞的杀伤力。

结果

与空白组比较，柚皮苷各剂量组MDA-MB-231细胞的EdU阳性率、OD

450

值和PCNA、B7H1、PD-1蛋白表达水平均显著降低，细胞凋亡率和p53、cGAS、STING蛋白表达水平均显著升高（

＜0.05）；RU.521组MDA-MB-231细胞上述指标的变化情况与柚皮苷各剂量组相反（

＜0.05）。与空白+NK组比较，经不同浓度柚皮苷处理后的MDA-MB-231细胞与NK细胞共孵育体系上清液中颗粒酶B、TNF-α、IFN-γ水平及NK细胞杀伤力均显著升高（

＜0.05），而经RU.521处理后的共孵育体系中的上述指标均显著降低（

＜0.05）。

结论

柚皮苷可通过激活cGAS-STING信号通路来抑制MDA-MB-231细胞增殖、免疫逃逸，诱导其凋亡。

Abstract

OBJECTIVE

To explore the effects of naringin on the proliferation， apoptosis and immune escape of breast cancer cells through the cyclic GMP-AMP synthase （cGAS）-stimulator of interferon gene （STING） signaling pathway.

METHODS

The human breast cancer cell line MDA-MB-231 was divided into blank group， naringin low-， medium-， and high-dose groups （50， 100 and 200 μmol/L）， RU.521 group （cGAS inhibitor， 1 μmol/L） and high-dose naringin+RU.521 group （200 μmol/L naringin+1 μmol/L RU.521）. After each group of cells was treated with their respective drug solutions for 48 h， the proliferation of MDA-MB-231 cells [measured by the positive rate of 5-ethynyl-2′-deoxyuridine （EdU） and the value of optical density （OD

450

）

]

， apoptosi

s status， as well as the protein expression levels of proliferating cell nuclear antigen （PCNA）， p53， B7 homolog 1 （B7H1）， programmed death-1 （PD-1）， cGAS， and STING in the cells were measured. The MDA-MB-231 cells of the above groups were treated with corresponding drugs for 48 h respectively， and then co-incubated with NK cells for 48 h except blank group. The levels of granzyme B， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ） in the supernatant of the co-incubation system and the killing power of NK cells were detected.

RESULTS

Compared with the blank group， the EdU positive rate， OD

450

value， and protein expression levels of PCNA， B7H1 and PD-1 in MDA-MB-231 cells of each dose group of naringin were significantly decreased， while the apoptotic rate and protein expression levels of p53， cGAS， and STING were significantly increased （

＜0.05）. The changes of the above indicators in the MDA-MB-231 cells of the RU.521 group were opposite to those in each naringin dose group （

＜0.05）. Compared with the blank+NK group， the levels of granzyme B， TNF-α， IFN-γ and the killing power of NK cells in the supernatant of the co-incubation system of MDA-MB-231 cells treated with different concentrations of naringin and NK cells were significantly increased （

＜0.05）. However， the above indicators in the co-incubation system of MDA-MB-231 cells treated with RU.521 and NK cells were significantly decreased （

＜0.05）.

CONCLUSIONS

Naringin can inhibit the proliferation and immune escape of MDA-MB-231 cells and induce their apoptosis by activating the cGAS-STING signaling pathway.

关键词

Keywords

references

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