Abstract
Objective:This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil(5-FU)and magnolol against cervical cancer.Methods:Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer.CCK-8 assay,colony formation assay,immunofluores-cence staining,adhesion assay,wound healing mobility assay,cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study.Results:Phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway was identified as the key pathway in silico study.The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation,induced the morphological change of HeLa cells by down-regulating the expression of α-actinin,tensin-2 and vin-culin.Moreover,magnolol enhanced inhibitory effect of 5-FU on the cell adhesion,migration and inva-sion.The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol.Moreover,the expression of E-cadherin and β-catenin was upregu-lated and the expression of Snail,Slug and vimentin was down-regulated by the 5-FU together with mag-nolol.Conclusion:Taken together,this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition(EMT)signaling pathways.
基金项目
Scientific Research Foundation of Jiangsu Province,China(BK20211327)
Jiangsu Province Traditional Chinese Medicine Science and Technology Project(2020ZX21)
Jiangsu Qinglian Project(2022)()
Yangzhou University Top Talent Project(2020)()
NETL
NSTL
万方数据