PMID- 38375055 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240221 IS - 2589-3610 (Electronic) IS - 1674-6384 (Print) IS - 1674-6384 (Linking) VI - 16 IP - 1 DP - 2024 Jan TI - Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways. PG - 94-105 LID - 10.1016/j.chmed.2023.01.004 [doi] AB - 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, immunofluorescence 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 alpha-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. 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 beta-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol. 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. CI - (c) 2023 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V. FAU - Chen, Yuanyuan AU - Chen Y AD - 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. FAU - Chen, Shanshan AU - Chen S AD - 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. FAU - Chen, Kaiting AU - Chen K AD - 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. FAU - Ji, Lanfang AU - Ji L AD - 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. FAU - Cui, Shuna AU - Cui S AD - 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. AD - Department of Gynecology and Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou 225009, China. LA - eng PT - Journal Article DEP - 20230525 PL - Singapore TA - Chin Herb Med JT - Chinese herbal medicines JID - 101556727 PMC - PMC10874772 OTO - NOTNLM OT - 5-fluorouracil OT - EMT pathway OT - PI3K/AKT/mTOR pathway OT - cervical cancer OT - magnolol OT - network pharmacology COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/20 11:51 MHDA- 2024/02/20 11:52 PMCR- 2023/05/25 CRDT- 2024/02/20 03:38 PHST- 2022/10/06 00:00 [received] PHST- 2022/11/29 00:00 [revised] PHST- 2023/01/16 00:00 [accepted] PHST- 2024/02/20 11:52 [medline] PHST- 2024/02/20 11:51 [pubmed] PHST- 2024/02/20 03:38 [entrez] PHST- 2023/05/25 00:00 [pmc-release] AID - S1674-6384(23)00054-0 [pii] AID - 10.1016/j.chmed.2023.01.004 [doi] PST - epublish SO - Chin Herb Med. 2023 May 25;16(1):94-105. doi: 10.1016/j.chmed.2023.01.004. eCollection 2024 Jan.