中国肺癌杂志2026，Vol.29Issue(4)：251-262,12.DOI:10.3779/j.issn.1009-3419.2026.102.10
地榆皂苷Ⅱ通过ITGB4/FAK信号通路抑制非小细胞肺癌的进展
Ziyuglycoside Ⅱ Inhibit the Progression of Non-small Cell Lung Cancer through the ITGB4/FAK Signaling Pathway
摘要
Abstract
Background and objective The incidence and mortality rates of non-small cell lung cancer(NSCLC)are generally on the rise,and the overall prognosis of patients remains poor.Current clinical treatment strategies have signifi-cant limitations.Notably,the bioactive components of traditional Chinese medicine possess unique advantages,including diverse targets of action and low toxicity.Ziyuglycoside II(ZGS II),a major active component of Sanguisorba officinalis L,has been shown to inhibit cancer cell proliferation,migration,and invasion.This property confers potential application value and developmental prospects for its use in cancer therapy.Nevertheless,the effects of ZGS II on NSCLC and the underlying mechanisms remain unclear.This study aimed to investigate the anti-tumor molecular mechanism of ZGS II in NSCLC and to explore the potential of being a novel therapeutic strategy for improving the prognosis of NSCLC patients.Methods First,the cell counting kit-8(CCK-8)and the colony formation assay were used to detect the changes in the viability and prolifera-tion ability of NSCLC cells after treatment with ZGS II.Wound-healing and Transwell assays were used to evaluate the effects of ZGS II on migration and invasion abilities.Western blot,Lentiviral transfection,wound healing assay,and Transwell assay were used to study the effects of ZGS II on the integrin β4/focal adhesion kinase(ITGB4/FAK)signaling pathway.A rescue experiment was then performed using the FAK agonist ZINC40099027.A nude mouse xenograftmodel was used to evaluate the inhibitory effect of ZGS II on NSCLC metastasis in vivo.Results ZGS II inhibited proliferation,migration,and invasion of NSCLC cells and suppressed the protein expression of ITGB4.This inhibitory effect was significantly enhanced upon ITGB4 knockdown.Meanwhile,total FAK expression remained nearly unchanged,but the protein expression level of phosphorylated focal adhesion kinase(p-FAK)was suppressed.Following the addition of an FAK activator,cell migration rate and the number of cells crossing the Transwell membrane increased,reversing the inhibitory effects of ZGS II on cell migration and invasion.Therefore,the anti-tumor effect of ZGS II depends on the reduced activation of the ITGB4/FAK signaling pathway.The nude mouse xenograftexperiment results showed that ZGS II effectively inhibited tumor growth in nude mice.Conclusion ZGS II inhibits proliferation,metastasis,and tumor growth in NSCLC by suppressing the ITGB4/FAK pathway.These findings high-light the potential of ZGS II as a promising drug for treating metastatic NSCLC and lay the foundation for its clinical research.关键词
肺肿瘤/地榆皂苷Ⅱ/ITGB4/FAK信号通路/进展Key words
Lung neoplasms/Ziyuglycoside Ⅱ/ITGB4/FAK pathway/Progression引用本文复制引用
任佳旋,刘雅妮,王博,吕嘉益,邸韫博,陈振文,徐义荣..地榆皂苷Ⅱ通过ITGB4/FAK信号通路抑制非小细胞肺癌的进展[J].中国肺癌杂志,2026,29(4):251-262,12.基金项目
本研究受山西省卫生健康委员会人才项目(No.2024224)和吕梁市分子病理重点实验室项目(No.ZDSYS06)资助 This study was supported by the grants from Talent Project of Shanxi Provincial Health Commission(No.2024224,to Yirong XU)and Key Laboratory of Molecular Pathology in Lvliang City(No.ZDSYS06,to Yirong XU). （No.2024224）
