南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (7): 1336-1344.doi: 10.12122/j.issn.1673-4254.2024.07.13

• • 上一篇    

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

黄燕1(), 覃璐璐1, 管少兴2, 管宴萍2, 韦玉茹2, 操艾伶2, 李冬梅3, 韦桂宁3(), 苏启表1()   

  1. 1.广东药科大学健康学院,广东 广州 510006
    2.中山大学药学院,广东 广州 510060
    3.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
  • 收稿日期:2023-12-21 出版日期:2024-07-20 发布日期:2024-07-25
  • 通讯作者: 韦桂宁,苏启表 E-mail:211214003@gdpu.edu.cn;weiguining2013@163.com;suqibiao@163.com
  • 作者简介:黄 燕,在读硕士研究生,E-mail: 211214003@gdpu.edu.cn
  • 基金资助:
    国家自然科学基金(81703769);广西人才基地项目(AD22035055);广东省自然科学基金(2019A1515011669)

Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways

Yan HUANG1(), Lulu QIN1, Shaoxing GUAN2, Yanping GUANG2, Yuru WEI2, Ailing CAO2, Dongmei LI3, Guining WEI3(), Qibiao SU1()   

  1. 1.College of Health Science, Guangdong Pharmaceutical University, Guangzhou 510006, China
    2.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510060, China
    3.Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning 530022, China
  • Received:2023-12-21 Online:2024-07-20 Published:2024-07-25
  • Contact: Guining WEI, Qibiao SU E-mail:211214003@gdpu.edu.cn;weiguining2013@163.com;suqibiao@163.com
  • Supported by:
    National Natural Science Foundation of China(81703769)

摘要:

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。

关键词: 金缕半枫荷, 胰腺癌, 网络药理学, 分子对接, 通路分析

Abstract:

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.

Key words: Semiliquidambar cathayensis Chang, pancreatic cancer, network pharmacology, molecular docking, pathway analysis