中国药理学通报2025，Vol.41Issue(10)：1940-1947,8.DOI:10.12360/CPB202504055
鸦胆子苦醇抑制STAT3磷酸化诱导小细胞肺癌凋亡
Brusatol induces apoptosis in small cell lung cancer by inhibiting STAT3 phosphorylation
摘要
Abstract
Aim To investigate the effect of Brusatol a-gainst small cell lung cancer(SCLC)and its potential mechanism.Methods CCK-8 assay and flow cytome-try were used to detect the cytotoxic effect of Brusatol on SCLC cells.Western blot was employed to measure the expression levels of apoptosis-related proteins,in-cluding cleaved poly(ADP-ribose)polymerase(cleaved-PARP),B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax).Network pharma-cology databases were utilized to identify common tar-gets of Brusatol,SCLC,and apoptosis.Kyoto Encyclo-pedia of Genes and Genomes(KEGG)and Gene On-tology(GO)enrichment analyses were performed on the intersecting genes.Molecular docking simulations between Brusatol and core targets were conducted using the CB-DOCK2 online platform to calculate binding en-ergies and sites.Western blot was further applied to detect the expression levels of signal transducer and ac-tivator of transcription 3(STAT3)and phosphorylated-STAT3(p-STAT3).Results Brusatol inhibited SCLC cell growth and induced apoptosis,significantly downregulating Bcl-2 and cleaved-PARP while upregu-lating Bax expression(P＜0.05).Network pharma-cology analysis revealed 108 common targets of Brusa-tol and SCLC,with the top three core targets being ep-idermal growth factor receptor(EGFR),STAT3,and tumor necrosis factor(TNF).Molecular docking re-sults indicated strong binding affinity between bruceine D and these core targets.Western blot validation con-firmed that bruceine D suppressed the expression of STAT3 and p-STAT3.Conclusion Brusatol exerts anti-SCLC effects by inhibiting STAT3 to induce apop-tosis in SCLC cells.关键词
鸦胆子苦醇/小细胞肺癌/凋亡/STAT3/网络药理学/分子对接Key words
Brusatol/small cell lung cancer/apopto-sis/STAT3/network pharmacology/molecular docking分类
医药卫生引用本文复制引用
韦惠兰,韦昕瑀,蒋木紫,韦姗姗,罗卓,阳洁..鸦胆子苦醇抑制STAT3磷酸化诱导小细胞肺癌凋亡[J].中国药理学通报,2025,41(10):1940-1947,8.基金项目
国家自然科学基金资助项目(No 8237142603,8216130319) （No 8237142603,8216130319）
广西研究生教育创新计划项目(No YCSW2024261) （No YCSW2024261）
广西自然科学基金杰出青年项目(No 2025GXNSFFA069017) （No 2025GXNSFFA069017）
广西自然科学基金重点项目(No 2023GXNSFDA026026) （No 2023GXNSFDA026026）
