首页|金缕半枫荷的水提取物抑制胰腺癌的作用机制:活性成分、关键靶点和信号通路

金缕半枫荷的水提取物抑制胰腺癌的作用机制:活性成分、关键靶点和信号通路

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目的 采用网络药理学及分子对接技术预测金缕半枫荷抗胰腺癌的关键靶点及信号通路,并通过胰腺癌细胞模型验证金缕半枫荷抗胰腺癌作用机制。方法 通过网络药理学数据库预测药物及疾病的靶点,构建蛋白互作网络图,分析通路、功能富集和分子对接。通过CCK-8法筛选金缕半枫荷对8种癌细胞的活性,并采用侵袭、迁徙、增殖、凋亡实验方法验证金缕半枫荷对胰腺癌的作用。采用Western blotting验证网络药理学的结果。结果 网络药理学共筛选得到金缕半枫荷活性成分18个,调控胰腺癌的潜在关键靶点21个。生物富集结果主要与蛋白质的磷酸化、信号传导、细胞凋亡等有关,通路主要与癌症信号通路、PI3K-Akt信号通路等有关。金缕半枫荷对胰腺癌细胞最敏感且显著抑制胰腺癌细胞Panc-1侵袭、迁徙和增殖,并且促进细胞凋亡(P<0。05)。Western blotting结果表明金缕半枫荷可以显著抑制PI3K和AKT的磷酸化水平(P<0。001)。结论 金缕半枫荷通过多成分、多靶点、多通路发挥抗胰腺癌作用,其中抑制PI3K-Akt通路是其机制之一。
Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer:the active components,therapeutic targets and pathways
Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Semiliquidambar cathayensis Changpancreatic cancernetwork pharmacologymolecular dockingpathway analysis

黄燕、覃璐璐、管少兴、管宴萍、韦玉茹、操艾伶、李冬梅、韦桂宁、苏启表

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广东药科大学健康学院,广东 广州 510006

中山大学药学院,广东 广州 510060

广西壮族自治区中医药研究院广西中药质量标准研究重点实验室,广西 南宁 530022

金缕半枫荷 胰腺癌 网络药理学 分子对接 通路分析

国家自然科学基金广西人才基地项目广东省自然科学基金

81703769AD220350552019A1515011669

2024

南方医科大学学报
南方医科大学

南方医科大学学报

CSTPCD北大核心
影响因子:1.654
ISSN:1673-4254
年,卷(期):2024.44(7)