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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
Δ

白文辉 ，李 英，李宗龙（青海红十字医院乳腺外科，西宁 810000）
＊

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2025）16-2012-05
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（OD450 ）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、
OD450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（P＜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（P＜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（P＜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（P＜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。
关键词 柚皮苷；乳腺癌；凋亡；增殖；免疫逃逸

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（Dept. of Breast Surgery， Qinghai Red Cross Hospital， Qinghai Xining
810000， China）

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 （OD450 ）]， apoptosis
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， OD450 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 （P＜
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 （P＜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 （P＜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 （P＜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.
KEYWORDS naringin； breast cancer； apoptosis； proliferation；
Δ 基金项目 青海省卫生健康科研项目（No.2024-wjzdx-120）
immune escape
＊第一作者 副主任医师。研究方向：乳腺肿瘤的相关治疗。E-
mail：yangkuang05743@163.com

· 2012 · China Pharmacy 2025 Vol. 36 No. 16 中国药房 2025年第36卷第16期