中国实验方剂学杂志2026，Vol.32Issue(10)：46-57,12.DOI:10.13422/j.cnki.syfjx.20251721
氧化白藜芦醇通过PI3K/Akt信号通路抑制非小细胞肺癌上皮间充质转化的机制
Mechanisms of Oxyresveratrol in Inhibiting Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer via PI3K/Akt Signaling Pathway
摘要
Abstract
Objective:To investigate the mechanisms by which oxyresveratrol(OXY)inhibits epithelial-mesenchymal transition(EMT)in non-small cell lung cancer(NSCLC)through the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods:Cell counting kit-8(CCK-8)assays were used to determine the survival rates of A549 and H1299 cells treated with different concentrations of OXY,and appropriate concentrations(0,30,60,90 μmol·L-1)were selected.The effects of OXY on the proliferation of A549 and H1299 cells were evaluated using 5-ethynyl-2'-deoxyuridine(EdU)assays and colony formation assays.Wound healing assays and Transwell invasion assays were performed to assess the effects of OXY on cell migration and invasion.Western blot(WB)was used to detect the expression levels of Snail,E-cadherin,N-cadherin,and Vimentin in A549 and H1299 cells.Network pharmacology and molecular docking were applied to predict the mechanism of action of OXY,and WB was used to evaluate the effects of OXY on proteins in the PI3K/Akt signaling pathway.Rescue experiments were conducted using the PI3K/Akt signaling pathway agonist 740Y-P.Under activation of the PI3K/Akt pathway,the effect of OXY on proliferation,migration,and invasion phenotypes,as well as on the expression levels of PI3K/Akt pathway-related proteins and EMT markers(Snail,E-cadherin,N-cadherin,and Vimentin),were examined.Results:In the forward experiments,CCK-8 assay results showed that,compared with the control group,the survival rates of NSCLC cells in the OXY-treated groups(20-120 μmol·L-1)were significantly decreased(P＜0.05).The half-maximal inhibitory concentration(IC50)values of A549 and H1299 cells after 48 h of OXY treatment were 113.6 μmol·L-1 and 92.53 μmol·L-1,respectively.Therefore,concentrations of 0,30,60,90 μmol·L-1 were selected as the gradient for subsequent phenotypic and mechanistic studies.Compared with the control group,the proliferation rate,colony number,migration rate,and invasion number of NSCLC cells in the OXY groups(30,60,and 90 μmol·L-1)were significantly decreased(P＜0.01,P＜0.05).WB results showed that,compared with the control group,the protein expression levels of Snail,N-cadherin,and Vimentin in NSCLC cells of the OXY groups were significantly decreased(P＜0.05),whereas E-cadherin expression was significantly increased(P＜0.01).Network pharmacology and molecular docking results indicated that OXY could act on the PI3K/Akt signaling pathway and exhibited good binding affinity with PI3K and Akt proteins.Further WB results showed that,compared with the control group,there were no statistically significant differences in the expression levels of PI3K and Akt proteins in NSCLC cells of the OXY groups,whereas the expression levels of phosphorylated PI3K(p-PI3K)and phosphorylated Akt(p-Akt)were significantly decreased(P＜0.05).In the rescue experiments,compared with the control group,the proliferation rate,colony number,migration rate,and invasion number of NSCLC cells in the 740Y-P group(15 μmol·L-1)were significantly increased(P＜0.01).Compared with the control+OXY group(90 μmol·L-1),these indices in the 740Y-P+OXY group(15 μmol·L-1+90 μmol·L-1)were also significantly increased(P＜0.01).WB results showed that,compared with the control group,there were no statistically significant differences in the expression levels of PI3K and Akt proteins in the 740Y-P group.However,the expression levels of p-PI3K,p-Akt,Snail,N-cadherin,and Vimentin were significantly increased(P＜0.05),while E-cadherin expression was significantly decreased(P＜0.01).Compared with the control+OXY group,there were no statistically significant differences in PI3K and Akt protein expression in the 740Y-P+OXY group.However,the expression levels of p-PI3K,p-Akt,Snail,N-cadherin,and Vimentin were significantly increased(P＜0.05),while E-cadherin expression was significantly decreased(P＜0.05).Conclusion:OXY inhibits the PI3K/Akt signaling pathway and suppresses the EMT process,thereby exerting anti-metastatic effects in NSCLC.关键词
非小细胞肺癌/氧化白藜芦醇/磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)/上皮-间充质转化(EMT)/增殖与侵袭Key words
non-small cell lung cancer/oxyresveratrol/phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)/epithelial-mesenchymal transition(EMT)/proliferation and invasion分类
医药卫生引用本文复制引用
胡林凌,江波,齐淯,邹义龙,范存愈,范艺龄,余贻汉,徐波..氧化白藜芦醇通过PI3K/Akt信号通路抑制非小细胞肺癌上皮间充质转化的机制[J].中国实验方剂学杂志,2026,32(10):46-57,12.基金项目
湖北省中医药管理局重点项目(ZY2023Z003) （ZY2023Z003）
国家自然科学基金项目(82305228) （82305228）
