中国实验方剂学杂志2026，Vol.32Issue(10)：23-33,11.DOI:10.13422/j.cnki.syfjx.20260622
丹酚酸B通过下调PAICS表达抑制非小细胞肺癌上皮间质转化机制
Mechanisms of Salvianolic Acid B in Inhibiting Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Downregulating PAICS Expression
摘要
Abstract
Objective:To investigate the molecular mechanisms by which salvianolic acid B(SalB)inhibits epithelial-mesenchymal transition(EMT)in non-small cell lung cancer(NSCLC)by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase(PAICS)expression.Methods:NSCLC A549 cells and normal bronchial epithelial cells(bronchial epithelium transformed with Ad12-SV40 2B,BEAS-2B)were used as models.Cell viability was assessed using the cell counting kit-8(CCK-8)assay after treatment with SalB(0,50,100,200,300,400,500 μmol·L-1 for 24 or 48 h to determine effective and safe intervention concentrations.Cell proliferation,cell cycle distribution,and apoptosis were evaluated by 5-ethynyl-2'-deoxyuridine(EdU)staining and flow cytometry,respectively.Wound healing and Transwell invasion assays were performed to assess cell migration and invasion.RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment.Molecular docking was used to predict the binding ability between SalB and PAICS,and the cellular thermal shift assay(CETSA)was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein.Western blot(WB)was used to detect the effects of SalB on PAICS and EMT-related proteins(E-cadherin,N-cadherin,Vimentin,Snail,and Slug).A functional rescue assay was conducted by PAICS overexpression via plasmid transfection.Results:Compared with the control group,SalB inhibited A549 cell viability in a dose-dependent manner(P＜0.05),and the effective concentrations(≤300 μmol·L-1)showed no significant cytotoxicity in BEAS-2B cells.Within this concentration range,SalB significantly inhibited A549 cell proliferation,migration,and invasion,and induced G0/G1 phase arrest and apoptosis(P＜0.05).Transcriptomic analysis showed that SalB significantly downregulated PAICS expression,and its functions were enriched in cell proliferation and EMT.Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis(P＜0.01).Molecular docking showed that SalB has strong binding ability to PAICS(binding energy-9.1 kcal·mol-1.CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein(P＜0.05).WB results showed that,compared with the control group,SalB dose-dependently downregulated PAICS expression,upregulated E-cadherin,and downregulated N-cadherin,Vimentin,Snail,and Slug(P＜0.05).Functional rescue experiments showed that,compared with the empty vector group,PAICS overexpression significantly enhanced A549 cell proliferation,migration,and invasion,promoted cell cycle progression,and inhibited apoptosis(P＜0.05).Meanwhile,compared with the empty vector+SalB-H group,PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins(N-cadherin,Vimentin,Snail,and Slug),and downregulated E-cadherin expression(P＜0.05,P＜0.01),indicating that PAICS is a key functional target mediating the antitumor effects of SalB.Conclusion:SalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression,thereby exerting anti-NSCLC effects.This study not only reveals that PAICS is a key functional target through which SalB regulates EMT,but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.关键词
非小细胞肺癌/丹酚酸B/磷酸核糖氨基咪唑丁酰胺合成酶/上皮间质转化/迁移与侵袭Key words
non-small cell lung cancer/salvianolic acid B/phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase/epithelial-mesenchymal transition/migration and invasion分类
医药卫生引用本文复制引用
徐波,张继先,胡林凌,江波,袁沙沙,范艺龄,阮梽珅,余贻汉,苗青..丹酚酸B通过下调PAICS表达抑制非小细胞肺癌上皮间质转化机制[J].中国实验方剂学杂志,2026,32(10):23-33,11.基金项目
湖北省中医药管理局重点项目(ZY2023Z003) （ZY2023Z003）
国家优势专科建设项目(fm20242503) （fm20242503）
中国中医科学院西苑医院名老中医药专家学术经验传承项目(XYZX0101-38) （XYZX0101-38）
国家自然科学基金项目(82305228) （82305228）
