南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (9): 2206-2221.doi: 10.12122/j.issn.1673-4254.2026.09.19

• • 上一篇    

黄芪注射液通过多成分靶向CCL2/FOS/PPARG/CXCL8抑制宫颈癌恶性进展

马园园1,3(), 刘悦1(), 高宁1,2(), 霍宇萌1, 陈美霓1,2, 李佳文1, 刘佳浩1, 张满秋1, 严冰冰1, 许诺1, 赵菊梅1,2()   

  1. 1.延安大学延安医学院基础医学院,陕西 延安 716000
    2.延安市陕北肿瘤防治重点实验室,延安大学延安医学院基础医学院,陕西 延安 716000
    3.延安大学附属医院妇科,陕西 延安 716000
  • 收稿日期:2025-12-04 出版日期:2026-09-20 发布日期:2026-09-30
  • 通讯作者: 赵菊梅 E-mail:304769958@qq.com;liuyue10222001@163.com;yadxgaoning@163.com;jmz2003.stu@163.com
  • 作者简介:马园园,在读硕士研究生,主治医师,E-mail: 304769958@qq.com
    刘 悦,在读硕士研究生,E-mail: liuyue10222001@163.com
    高 宁,博士,讲师,硕士生导师,E-mail: yadxgaoning@163.com
    第一联系人:(马园园、刘 悦、高 宁并列第一作者)
  • 基金资助:
    陕西省教育厅专项科研计划项目(23JK0732);陕西省科技厅科技资源开放共享平台(2024CX-GXPT-27);陕西省大学生创新创业计划训练项目(S202410719094);陕西省大学生创新创业计划训练项目(S202510719111);延安市科技计划项目(2023-SFGG-098);延安市科学技术协会青年人才托举计划项目(2023-20-1)

Multiple components in Astragalus Injection target CCL2/FOS/PPARG/CXCL8 to suppress cervical cancer progression

Yuanyuan MA1,3(), Yue LIU1(), Ning GAO1,2(), Yumeng HUO1, Meini CHEN1,2, Jiawen LI1, Jiahao LIU1, Manqiu ZHANG1, Bingbing YAN1, Nuo XU1, Jumei ZHAO1,2()   

  1. 1.School of Basic Medical Sciences, Yan'an Medical College, Yan'an University, Yan'an 716000, China
    2.Key Laboratory of Northern Shaanxi Cancer Prevention and Treatment, School of Basic Medical Sciences, Yan'an Medical College, Yan'an University, Yan'an 716000, China
    3.Department of Gynecology, Affiliated Hospital of Yan'an University, Yan'an 716000, China
  • Received:2025-12-04 Online:2026-09-20 Published:2026-09-30
  • Contact: Jumei ZHAO E-mail:304769958@qq.com;liuyue10222001@163.com;yadxgaoning@163.com;jmz2003.stu@163.com

摘要:

目的 预测黄芪注射液在抗宫颈癌中的作用靶标及分子机制。 方法 通过STRING、Cytoscape构建黄芪注射液与宫颈癌的交集靶点网络,筛选关键靶标;DAVID数据库完成靶点GO功能注释与KEGG通路富集分析;分子对接分析药物活性成分与核心靶点的结合能力;通过CCK-8、细胞克隆、划痕、Transwell检测黄芪注射液对人宫颈癌SiHa细胞增殖、迁移、侵袭影响;Western blotting检测核心靶点FOS、PPARG、CXCL8、CCL2,IL-17通路核心分子NF-κB p65、p-p65、STAT3、p-STAT3及细胞凋亡相关蛋白BAX、BCL2、Caspase-3、cleaved-Caspase-3的表达。考马斯亮蓝与鬼笔环肽染色检测细胞骨架微丝变化;JC-10检测线粒体膜电位;AO/EB染色检测细胞凋亡及细胞膜通透性。构建U14宫颈癌荷瘤小鼠模型,8 只荷瘤小鼠随机分为对照组和黄芪注射液处理组,4只/组;测量肿瘤体积生长情况;HE染色分析肿瘤组织病理学;免疫组织化学染色观察CCL2、PPARG、FOS阳性表达率。 结果 确定黄芪注射液中5个活性成分与宫颈癌关键靶点CCL2、CXCL8、FOS、PPARG,且分子对接结合能均小于-5 kJ/mol。细胞实验结果显示黄芪注射液能显著抑制宫颈癌细胞的增殖、迁移和侵袭能力(P<0.05),并引起微丝结构改变,诱导细胞发生凋亡,靶点蛋白FOS、CXCL8、CCL2、PPARG、抗凋亡蛋白 BCL2 及磷酸化的p-p65 (Ser536)、p-STAT3 (Tyr705)蛋白表达水平下调(P<0.01),而促凋亡蛋白BAX、cleaved-Caspase-3表达水平升高(P<0.001)。体内实验结果显示,黄芪注射液可抑制宫颈癌移植瘤增殖,引起肿瘤组织大片坏死,使核心靶点蛋白CCL2、PPARG、FOS阳性表达下调(P<0.001)。 结论 黄芪注射液可通过多个活性成分抑制宫颈癌细胞中多靶点蛋白表达,引起微丝结构损伤,导致癌细胞运动能力减弱及细胞凋亡。深入研究黄芪注射液抗宫颈癌的有效成分和作用机制,为黄芪注射液在宫颈癌治疗领域的研究开辟新视角。

关键词: 黄芪注射液, 宫颈癌, 网络药理学, 微丝, 细胞凋亡

Abstract:

Objective To predict the functional targets and molecular mechanisms of Astragalus Injection for suppressing cervical cancer. Methods The overlapping targets between Astragalus Injection and cervical cancer were used to construct a protein-protein interaction network. GO functional annotation and KEGG pathway enrichment analysis were performed, and molecular docking study was conducted to evaluate the binding capacity between drug active components and the core targets. SiHa cells were treated with Astragalus Injection and the changes in cell proliferation, migration and invasion were examined. The expressions of the core targets (FOS, PPARG, CXCL8, and CCL2), key molecules in the IL-17 pathway (NF-κB p65, p-p65, STAT3, and p-STAT3), Bax, Bcl-2, caspase-3, and cleaved caspase-3 were detected in the treated cells. The changes in microfilament, mitochondrial membrane potential, cell apoptosis and membrane permeability were observed using Coomassie brilliant blue, phalloidin, JC-10 and AO/EB staining. In a mouse model bearing U14 cervical cancer xenograft, the effect of Astragalus Injection on tumor growth was observed, tumor histopathology was examined using HE staining, and CCL2, PPARG and FOS expressions were analyzed with immunohistochemistry. Results Five major active components of Astragalus Injection were found to stably bind to 4 core targets (CCL2, CXCL8, FOS, and PPARG) with docking binding energies all below -5 kJ/mol. Astragalus Injection significantly inhibited the proliferation, migration and invasion of SiHa cells, disrupted cytoskeletal microfilament structure, and induced cell apoptosis, causing also significantly lowered protein levels of FOS, CXCL8, CCL2, PPARG, Bcl-2, p-p65 and p-STAT3 and increased expressions of Bax and cleaved caspase-3. In the tumor-bearing mice, Astragalus Injection significantly suppressed xenograft growth, induced tumor tissue necrosis, and reduced the expressions of CCL2, PPARG and FOS. Conclusion Astragalus Injection inhibits cervical cancer progression by downregulating multiple target proteins, damaging microfilament structure, weakening tumor cell motility and promoting apoptosis.

Key words: Astragalus injection, cervical cancer, network pharmacology, microfilament, cell apoptosis