基于网络药理学探讨姜黄素抗人喉癌细胞的分子机制及其实验研究*
DOI:
作者:
作者单位:

1.兰州大学第一临床医学院;2.甘肃省人民医院

作者简介:

通讯作者:

基金项目:

国家自然科学(No. 81860475);甘肃省人民医院国家科研项目培养计划重点项目 (No. 19SYPYA-13) ;甘肃中医药大学科学研究与创新(No.2020KCZD-7)


Molecular mechanism and experimental study of curcumin anti-human laryngeal cancer cells based on network pharmacologyJiang Xuelian1;Wei Xudong1,2;Xu Xiaoyan3;Ma Binjuan2;Cao Jiyan4;Zhang Jingyue1
Author:
Affiliation:

The First Clinical Medical College of LanZhou University

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
    摘要:

    目的:基于网络药理学探讨姜黄素抗喉癌的关键靶点并设计实验加以验证。方法:姜黄素靶点通过Swiss Target Prediction与PharmMapper数据库进行筛选,采用GeneCards、OMIM数据库筛选喉癌靶点,通过FunRich软件获得共有靶点,使用DAVID平台对姜黄素-喉癌共有靶点进行基因本体生物进程及京都基因与基因组百科全书通路分析,基于Cytoscape软件进行关键靶点筛选,采用分子对接对关键靶点进行验证分析,细胞划痕实验观察姜黄素对喉癌细胞迁移能力的影响,CCK-8法检测姜黄素对细胞增殖能力的影响及对化疗药物多柔比星的化疗增效作用,Western Blot检测姜黄素对喉癌细胞P-STAT3蛋白表达水平的影响。结果:获得5个靶点,KEGG通路富集分析发现与喉癌相关信号通路为癌症中的蛋白多糖通路、TNF信号传导通路、癌症中的通路、HIF-1信号传导通路、Jak-STAT信号传导通路、癌症中的碳代谢通路、血管内皮生长因子信号传导途径,通过分子对接发现:姜黄素与STAT3、P-STAT3有较好的结合,细胞划痕实验观察到姜黄素可抑制喉癌细胞的迁移能力,CCK-8法发现姜黄素可明显抑制喉癌细胞的体外增殖活性,且姜黄素对化疗药多柔比星具有化疗增效作用;Western blot实验发现随着姜黄素浓度的提高不同程度的抑制喉癌细胞P-STAT3蛋白的表达。结论:姜黄素呈剂量依赖性抑制喉癌细胞的增殖、迁移;姜黄素对化疗药物多柔比星具有化疗增效作用;姜黄素通过调节EGFR、 STAT3、EP300及P-STAT3抗喉癌肿瘤细胞,已验证的靶点为P-STAT3。

    Abstract:

    OBJECTIVE: To investigate the key targets of curcumin against laryngeal cancer based on network pharmacology and to design experiments to verify them. METHODS: Curcumin targets were screened by Swiss Target Prediction, laryngeal cancer targets were screened by GeneCards, OMIM and TTD databases, shared targets were obtained by FunRich software, gene ontology biological processes and Kyoto Gene and Genome Encyclopedia pathways were performed on curcumin-laryngeal cancer shared targets using DAVID platform. The effect of curcumin on the migration ability of laryngeal cancer cells was observed by cell scratching assay, the effect of curcumin on cell proliferation ability and its chemotherapeutic potentiation effect on chemotherapeutic drug doxorubicin was detected by CCK-8 method, and the effect of curcumin on the expression level of P STAT3 protein expression level in laryngeal cancer cells. Results: Five targets were obtained, and KEGG pathway enrichment analysis revealed that the signaling pathways related to laryngeal cancer were proteoglycan pathway in cancer, TNF signaling pathway, pathway in cancer, HIF-1 signaling pathway, Jak-STAT signaling pathway, carbon metabolism pathway in cancer, and vascular endothelial growth factor signaling pathway, and it was found by molecular docking that: curcumin binds well to STAT3, P- STAT3, cell scratch assay observed that curcumin could inhibit the migration ability of laryngeal cancer cells, CCK-8 method found that curcumin could significantly inhibit the proliferation activity of laryngeal cancer cells in vitro, and curcumin had a chemotherapeutic potentiation effect on chemotherapeutic drug doxorubicin; Western blot assay found that as the concentration of curcumin increased to different degrees to inhibit the expression of P-STAT3 protein expression.Conclusion: Curcumin inhibited the proliferation and migration of laryngeal cancer cells in a dose-dependent manner; curcumin had a chemotherapeutic potentiation effect on the chemotherapeutic drug doxorubicin; curcumin inhibited laryngeal cancer tumor cells by regulating EGFR, STAT3, EP300 and P-STAT3, and the validated target was P-STAT3.

    参考文献
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2021-11-11
  • 最后修改日期:2022-01-31
  • 录用日期:2022-02-10
  • 在线发布日期:
温馨提示

本刊唯一投稿网址:www.xyosbs.com
唯一办公邮箱:xyent@126.com
编辑部联系电话:0731-84327210,84327469
本刊从未委托任何单位、个人及其他网站代理征稿及办理其他业务联系,谨防上当受骗!

关闭