Chen Yuanyuan, Chen Shanshan, Chen Kaiting, Ji Lanfang, Cui Shuna
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.
Chin Herb Med. 2023 May 25;16(1):94-105. doi: 10.1016/j.chmed.2023.01.004. eCollection 2024 Jan.
This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil (5-FU) and magnolol against cervical cancer.
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 study.
Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was identified as the key pathway 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 -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 -catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.
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.
本研究旨在探讨5-氟尿嘧啶（5-FU）与厚朴酚联合抗宫颈癌协同作用的作用模式。
采用网络药理学方法预测5-FU联合厚朴酚抗宫颈癌的分子机制。进行CCK-8法、集落形成试验、免疫荧光染色、黏附试验、伤口愈合迁移试验、细胞迁移和侵袭试验以及蛋白质印迹分析以验证研究结果。
磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）信号通路被确定为该研究的关键通路。实验结果表明，5-FU联合厚朴酚强烈抑制宫颈癌细胞增殖，通过下调α-辅肌动蛋白、张力蛋白-2和纽蛋白的表达诱导HeLa细胞形态改变。此外，厚朴酚增强了5-FU对细胞黏附、迁移和侵袭的抑制作用。5-FU与厚朴酚联合强烈抑制AKT和PI3K的磷酸化以及mTOR的表达。此外，5-FU与厚朴酚上调E-钙黏蛋白和β-连环蛋白的表达，下调Snail、Slug和波形蛋白的表达。
综上所述，本研究表明5-FU联合厚朴酚通过调节PI3K/AKT/mTOR和上皮-间质转化（EMT）信号通路发挥协同抗宫颈癌作用。
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