南京中医药大学学报2025，Vol.41Issue(8)：1037-1046,10.DOI:10.14148/j.issn.1672-0482.2025.1037
基于AKT/S6K1信号通路探讨白术内酯Ⅰ抑制结直肠癌的作用机制
Investigation of the Mechanism of Atractylodes Ⅰ Inhibiting Colorectal Cancer via the AKT/S6K1 Signaling Pathway
摘要
Abstract
OBJECTIVE To investigate the pharmacological efficacy and mechanism of action of Atractylenolide Ⅰ(Atr-Ⅰ)in inhibiting colorectal cancer.METHODS Among three active compounds of Atractylodes macrocephala,Atr-Ⅰ exhibited the highest anti-tumor potency by MTT assay.The optimal concentration of Atr-Ⅰ was determined.The effect of Atr-Ⅰ on LoVo cell prolifera-tion was assessed via a clonogenic assay,while its impact on apoptosis and cell cycle progression was evaluated using flow cytometry.The influence of Atr-Ⅰ on the migration and invasion of LoVo cell line was examined through wound healing and Transwell migration assays.Western blot analysis was performed to explore the effects and mechanisms of Atr-Ⅰ on proteins associated with mi-gration,proliferation,and epithelial-mesenchymal transition(EMT)in LoVo cells.The CT26 mouse subcutaneous tumor model was established,and histopathological analysis was conducted using hematoxylin-eosin(HE)staining.Western blot was also used to assess the effects of Atr-Ⅰ on EMT-related proteins in mouse tissues to elucidate underlying mechanisms.RESULTS Atr-Ⅰ significantly reduced colorectal cancer cell viability,with statistically significant differences between treatment and control groups(P<0.05,P<0.01).Atr-Ⅰ induced apoptosis in LoVo cells,with the treatment group showing significant differences compared to the control(P<0.05,P<0.01).Cell cycle analysis revealed that Atr-Ⅰ exerted anti-tumor effects by inducing G2/M phase arrest,with increased G2 phase cell numbers in the LoVo treatment group compared to the control(P<0.05).Wound healing and Transwell migration assays confirmed that Atr-Ⅰ significantly inhibited tumor cell migration and invasion(P<0.05,P<0.01).Western blot analysis demonstra-ted that Atr-Ⅰ specifically suppressed the expression of c-Myc and Bcl-2(P<0.05),as well as cell cycle-related proteins CDK1,Cyclin B1,and Cyclin D1(P<0.05),and angiogenesis-related proteins VEGF and MMP9(P<0.05).Additionally,Atr-Ⅰ down-regulated EMT-related protein N-cadherin and upregulated E-cadherin expression(P<0.05).It also reduced the expression of p-AKT and p-S6K1(P<0.05).CONCLUSION Atr-Ⅰ exhibits potent anti-tumor effects against colorectal cancer,potentially through modulation of the AKT/S6K1 signaling pathway.关键词
白术内酯Ⅰ/结直肠癌/AKT/S6K1信号通路/上皮间质转化/LoVo细胞/CT26小鼠Key words
Atractylenolide Ⅰ/colorectal cancer/AKT/S6K1 signaling pathway/epithelial-mesenchymal transition/LoVo cells/CT26 mice分类
医药卫生引用本文复制引用
田薇,闫秋莹,罗婧雯,吴其标,沈卫星,程海波,徐长亮,孙东东..基于AKT/S6K1信号通路探讨白术内酯Ⅰ抑制结直肠癌的作用机制[J].南京中医药大学学报,2025,41(8):1037-1046,10.基金项目
国家自然科学基金面上项目(82374287) （82374287）
国家自然科学基金国际(地区)合作与交流项目(82361168663) （地区）
江苏省中医药领军人才培养项目(SLJ0312) （SLJ0312）
