首页|Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways

Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways

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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.

cervical cancer5-fluorouracilEMT pathwaymagnololnetwork pharmacologyPI3K/AKT/mTOR pathway

Yuanyuan Chen、Shanshan Chen、Kaiting Chen、Lanfang Ji、Shuna Cui

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Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases,Medical College of Yangzhou University,Yangzhou 225009,China

Department of Gynecology and Obstetrics,Affiliated Hospital of Yangzhou University,Yangzhou 225009,China

Scientific Research Foundation of Jiangsu Province,ChinaJiangsu Province Traditional Chinese Medicine Science and Technology ProjectJiangsu Qinglian Project(2022)Yangzhou University Top Talent Project(2020)

BK202113272020ZX21

2024

10.1016/j.chmed.2023.01.004

中草药(英文版)
天津药物研究院 中国医学科学院药用植物研究所

中草药(英文版)

CSTPCD
影响因子：0.6
ISSN：1674-6384
年,卷(期)：2024.16(1)
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