基于网络药理学及体外细胞学探讨野黄芩苷抑制口腔白斑癌变的作用机制

doi:10.19439/j.sjos.2023.06.003

上海口腔医学 ›› 2023, Vol. 32 ›› Issue (6): 572-577.doi: 10.19439/j.sjos.2023.06.003

基于网络药理学及体外细胞学探讨野黄芩苷抑制口腔白斑癌变的作用机制

叶赛¹, 张颖¹, 夏荣辉², 周永梅¹, 吴岚¹

1.上海交通大学医学院附属第九人民医院口腔黏膜病科,2.口腔病理科,上海交通大学口腔医学院, 国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室, 上海市口腔医学研究所,上海 200011

收稿日期:2023-01-13 修回日期:2023-03-10 出版日期:2023-12-15 发布日期:2024-01-12
通讯作者: 吴岚,E-mail: teana_wu@sina.com
作者简介:叶赛（1997-）,女,硕士,E-mail: 1085012740@qq.com
基金资助:
上海市科委基金（21S21902000）; 上海市卫健委、上海市中医药管理局重大疑难疾病中西医协同诊疗示范项目 [ZY(2021-2023)-0207-01-04]; 上海市卫健委中医药科研项目（2022CX009）; 上海交通大学医学院附属第九人民医院交叉基金（JYJC202111）

The mechanism of scutellarin inhibiting oral leukoplakia carcinogenesis based on network pharmacology and in vitro cytology

YE Sai¹, ZHANG Ying¹, XIA Rong-hui², ZHOU Yong-mei¹, WU Lan¹

1. Department of Oral Mucosal Diseases, 2. Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology.Shanghai 200011, China

Received:2023-01-13 Revised:2023-03-10 Online:2023-12-15 Published:2024-01-12

摘要/Abstract

摘要： 目的: 利用网络药理学分析野黄芩苷抑制口腔白斑（oral leukoplakia,OLK）癌变的分子机制,采用细胞学进一步验证。方法: 通过网络药理学挖掘野黄芩苷作用于OLK的分子靶点,构建蛋白互作网络,通过GO、KEGG富集分析预测野黄芩苷可能的作用靶点及相关通路。利用CCK-8实验、Transwell实验验证野黄芩苷对口腔白斑细胞（Leuk-1）、舌癌细胞（Cal-27）增殖、迁移、侵袭的作用;Western 印迹法检测相关分子的表达。采用GraphPad Prism 9软件包进行统计学分析。结果: 野黄芩苷作用于OLK的潜在作用靶点共29个,HIF-1α为其中关键靶点。GO、KEGG分析结果显示,野黄芩苷高度参与细胞及组织对缺氧的反应并作用于组织缺氧相关的HIF-1信号通路。细胞学结果表明,野黄芩苷能显著抑制Leuk-1、Cal-27增殖(IC₅₀：2 mmol/L)、迁移和侵袭（P<0.05）。Western印迹法进一步验证了关键分子靶点,1 mmol/L野黄芩苷能明显抑制Leuk-1和Cal-27细胞内HIF-1α蛋白的表达。结论: 野黄芩苷可能通过抑制HIF-1信号通路表达,对OLK癌变起到抑制作用。

关键词: 网络药理学, 野黄芩苷, 口腔白斑, 缺氧诱导因子

Abstract: PURPOSE: To investigate the potential mechanisms of scutellarin on oral leukoplakia (OLK) by network pharmacology and further verify by cytology. METHODS: The potential targets of scutellarin acting on OLK were excavated through network pharmacology. PPI network was constructed, and the possible targets and pathways of scutellarin were predicted by GO and KEGG enrichment analysis. CCK-8 and Transwell assays were used to verify the effects of scutellarin on proliferation, migration and invasion of Leuk-1 and Cal-27 cell lines. The expression of related molecules was detected by Western blot to explore potential molecular mechanisms. Statistical analysis was performed with GraphPad Prism 9 software package. RESULTS: There were 29 potential targets of scutellarin acting on OLK, of which HIF-1α was the key target, and the results of GO and KEGG analysis showed that scutellarin was highly involved in the response of cells and tissues to hypoxia and influenced HIF-1 signaling pathway. Scutellarin can significantly inhibit the proliferation (IC₅₀:2 mmol/L), invasion and migration of Leuk-1 and Cal-27 cells(P<0.05), and downregulated the expression of HIF-1α in Leuk-1 and Cal-27 cells. CONCLUSIONS: Scutellarin can inhibit carcinogenesis of OLK by suppressing HIF-1 signaling pathway.

Key words: Network pharmacology, Scutellarin, Oral leukoplakia, HIF-1α

中图分类号:

R781.5

叶赛, 张颖, 夏荣辉, 周永梅, 吴岚. 基于网络药理学及体外细胞学探讨野黄芩苷抑制口腔白斑癌变的作用机制[J]. 上海口腔医学, 2023, 32(6): 572-577.

YE Sai, ZHANG Ying, XIA Rong-hui, ZHOU Yong-mei, WU Lan. The mechanism of scutellarin inhibiting oral leukoplakia carcinogenesis based on network pharmacology and in vitro cytology[J]. Shanghai Journal of Stomatology, 2023, 32(6): 572-577.

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基于网络药理学及体外细胞学探讨野黄芩苷抑制口腔白斑癌变的作用机制

The mechanism of scutellarin inhibiting oral leukoplakia carcinogenesis based on network pharmacology and in vitro cytology

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