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Archive > Volume 16 Issue 1 > 2024,16(1):94-105. DOI:https://doi.org/10.1016/j.chmed.2023.01.004 Prev Next

厚樸酚協(xié)同5 -FU調(diào)控PI3K / AKT / mTOR和EMT通路抑制宮頸癌細胞轉移

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

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    摘要:
    目的：本研究旨在探討厚樸酚與5 -氟尿嘧啶 (5-FU) 協(xié)同抗宮頸癌的作用機制。 方法：采用網(wǎng)絡藥理學方法預測5 - FU聯(lián)合厚樸酚抗宮頸癌的分子機制。通過CCK - 8實驗、集落實驗、免疫熒光染色、黏附實驗、劃痕實驗、細胞遷移和侵襲實驗以及Western blot實驗驗證網(wǎng)絡藥理學結果。 結果：網(wǎng)絡藥理學研究結果提示：PI3K / AKT / mTOR信號通路為5 - FU聯(lián)合厚樸酚抗宮頸癌作用的關鍵通路。細胞實驗結果證明，厚樸酚聯(lián)合5 - FU顯著抑制宮頸癌細胞的增殖并誘導宮頸癌HeLa細胞形態(tài)變化，下調(diào)α-actinin, tensin-2和 vinculin表達。此外，厚樸酚可增強5 - FU對宮頸癌HeLa細胞黏附、遷移和侵襲能力的抑制作用。厚樸酚聯(lián)合5 - FU能抑制AKT、PI3K的磷酸化和mTOR的表達，并上調(diào)E-鈣E-cadherin 和 β-catenin的表達水平，下調(diào)snail、slug和vimentin的表達水平。 結論：本研究表明5 - FU聯(lián)合厚樸酚通過調(diào)控PI3K / AKT / mTOR和上皮間質(zhì)轉化 (EMT) 信號通路來發(fā)揮協(xié)同抗宮頸癌作用。

    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, 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.

    關鍵詞:
    關鍵詞：宮頸癌;5 -氟尿嘧啶;EMT通路;厚樸酚;網(wǎng)絡藥理學;PI3K / AKT / mTOR信號通路

    Keywords:


    Project Supported:
    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).

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