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 a-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 b-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.
This research was supported by the Scientific Research Foundation of Jiangsu Province, China (No. BK20211327) and Jiangsu Province Traditional Chinese Medicine Science and Technology Project (No. 2020ZX21), Jiangsu Qinglian Project (2022), and Yangzhou University Top Talent Project (2020).
Yuanyuan Chen a, Shanshan Chen a, Kaiting Chen a, Lanfang Ji a, Shuna Cui a, b,*. Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways[J]. Chinese Herbal Medicines (CHM),2024,16(1):94-105
