中国病理生理杂志2025，Vol.41Issue(9)：1738-1747,10.DOI:10.3969/j.issn.1000-4718.2025.09.009
黄芩素通过AKT/β-catenin信号通路抑制人胰腺癌Aspc-1和Bxpc-3细胞增殖、迁移和侵袭
Baicalein inhibits proliferation,migration and invasion of human pancre-atic cancer Aspc-1 and Bxpc-3 cells via AKT/β-catenin signaling pathway
摘要
Abstract
AIM:To investigate the antitumor activity and targets of baicalein(Bai)in pancreatic cancer using network pharmacology combined with in vitro and in vivo experiments.METHODS:The targets of Bai and pancreatic can-cer were analyzed via multi-data screening.A protein-protein interaction network was constructed using STRING,and core targets were identified via Cytoscape.Functional enrichment was analyzed by Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG).Antitumor effects of Bai were assessed in pancreatic cancer cells Aspc-1 and Bxpc-3 using MTT and colony formation assays for proliferation,flow cytometry for apoptosis and cell cycle analysis,and Transwell assays for migration and invasion.A xenograft tumor model was established to evaluate tumor proliferation,im-munohistochemistry was performed to detect the protein expression of AKT in tumor tissues,and Western blot was used to analyze the expression levels of AKT,β-catenin,N-cadherin and Slug.RESULTS:A total of 108 overlapping targets were identified between Bai and pancreatic cancer.Among these,7 core targets were recognized,including proto-onco-gene tyrosine-protein kinase Src,heat shock protein 90 alpha family class A member 1(HSP90AA1),estrogen receptor 1(ESR1),tumor protein p53(TP53),epidermal growth factor receptor(EGFR),AKT1,and mitogen-activated protein ki-nase 3(MAPK3).The GO analysis revealed significant enrichment in oxidative stress response,protein phosphorylation,and serine/threonine kinase activity.The KEGG analysis primarily enriched the PI3K/AKT,MAPK and Ras signaling pathways.The MTT and colony formation assays showed that Bai inhibited the viability of Aspc-1 and Bxpc-3 cells in a dose-dependent manner(72 h IC50 values were 73.6 µmol/L and 83.4 µmol/L,respectively)and reduced cell colony for-mation(P<0.05 or P<0.01).Flow cytometry confirmed that Bai induced apoptosis of Aspc-1 and Bxpc-3 cells(P<0.01)and blocked the cell cycle at the G0/G1 phase(P<0.05 or P<0.01).Transwell experiments indicated that Bai inhibited the migration and invasion of Aspc-1 and Bxpc-3 cells(P<0.05 or P<0.01).In vivo,Bai significantly inhibited the growth of Aspc-1 cell xenograft tumors(P<0.01).Immunohistochemistry revealed a significant reduction in AKT expression in tu-mor tissues(P<0.01),and Western blot showed decreased expression of AKT,β-catenin,N-cadherin and Slug in both Aspc-1 and Bxpc-3 cells(P<0.01).CONCLUSION:Baicalein inhibits pancreatic cancer cell proliferation,migration,and invasion,potentially through down-regulation of AKT,β-catenin,N-cadherin,and Slug expression.关键词
黄芩素/胰腺癌/网络药理学/AKT/β-catenin信号通路/细胞凋亡Key words
baicalein/pancreatic cancer/network pharmacology/AKT/β-catenin signaling pathway/apoptosis分类
医药卫生引用本文复制引用
陈晓亮,王琼,汤琳,殷丽丽,于金生,白云峰,秦一,冯锋..黄芩素通过AKT/β-catenin信号通路抑制人胰腺癌Aspc-1和Bxpc-3细胞增殖、迁移和侵袭[J].中国病理生理杂志,2025,41(9):1738-1747,10.基金项目
国家自然科学基金青年项目(No.82204523) （No.82204523）
山西省基础研究计划面上项目(No.202403021221179) （No.202403021221179）
大同市重点研发(社会发展)项目(No.2024044) （社会发展）
大同市应用基础研究项目(No.2024073) （No.2024073）
