|本期目录/Table of Contents|

[1]时伟峰,张宇凡,吴延升.基于网络药理学和分子对接预测环共诺醇治疗口腔鳞状细胞癌的分子机制[J].天津医科大学学报,2026,32(04):342-349.[doi:10.20135/j.issn.1006-8147.2026.04.0342]
　SHI Weifeng,ZHANG Yufan,WU Yansheng.Prediction of the molecular mechanism of Cyclocommunol in the treatment of oral squamous cell carcinoma based on network pharmacology and molecular docking[J].Journal of Tianjin Medical University,2026,32(04):342-349.[doi:10.20135/j.issn.1006-8147.2026.04.0342]
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基于网络药理学和分子对接预测环共诺醇治疗口腔鳞状细胞癌的分子机制(PDF)

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
32卷
期数:
2026年04期
页码:
342-349
栏目:
论著
出版日期:
2026-07-10

文章信息/Info

Title:
Prediction of the molecular mechanism of Cyclocommunol in the treatment of oral squamous cell carcinoma based on network pharmacology and molecular docking
文章编号:
1006-8147（2026）04-0342-08
作者:
时伟峰1; 张宇凡2; 吴延升1
（1.天津医科大学肿瘤医院头颈肿瘤科，天津300060；2.南开大学生命科学学院，天津 300071）
Author(s):
SHI Weifeng1;  ZHANG Yufan2;  WU Yansheng1
（1. Department of Head and Neck Oncology， Tianjin Medical University Cancer Institute & Hospital， Tianjin 300060， China； 2. College of Life Sciences， Nankai University， Tianjin 300071， China）
关键词:
环共诺醇; 口腔鳞状细胞癌; 网络药理学; 分子对接; 细胞凋亡
Keywords:
Cyclocommunol;  oral squamous cell carcinoma;  network pharmacology;  molecular docking;  apoptosis
分类号:
R739.8
DOI:
10.20135/j.issn.1006-8147.2026.04.0342
文献标志码:
A
摘要:
目的：基于网络药理学与分子对接预测环共诺醇治疗口腔鳞状细胞癌（OSCC）的潜在靶点与通路。方法：通过多个在线数据库全面检索环共诺醇的作用靶点及OSCC相关疾病靶点，并通过Venn分析筛选二者交集靶点。构建交集靶点的蛋白互作（PPI）网络，利用Cytoscape软件及MCODE聚类算法识别关键基因模块。对筛选出的核心靶点进行Gene Ontology（GO）功能注释及通路富集（KEGG）分析，以揭示其涉及的生物学过程与信号通路。进一步开展分子对接分析，评估环共诺醇与核心靶点蛋白之间的结合能和结合模式，从结构层面验证其潜在活性。选取小鼠头颈鳞癌细胞（SCC-15），分为Control组、环共诺醇低浓度组（5 μmol/L）、环共诺醇高浓度组（ 10 μmol/L），通过CCK-8、免疫荧光及活性氧簇（ROS）检测实验评估环共诺醇对SCC-15细胞生物学行为的影响。结果：共筛选获得5 912个OSCC相关靶点与100个环共诺醇靶点，交集分析得到81个共同靶点。PPI网络分析基于MCC算法识别出 10 个核心靶点，包括 AKT1、ESR1、BCL2、CTNNB1、HSP90AA1、NFKB1、HSP90AB1、BCL2L1、HDAC1 和 EP300，这些靶点在肿瘤细胞增殖、凋亡与炎症反应中具有关键调控作用。GO与KEGG富集结果显示，环共诺醇的潜在作用主要涉及磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路、雌激素信号通路、核因子（NF）-κB相关通路以及凋亡和细胞周期调控等关键生物过程。分子对接结果进一步表明环共诺醇与核心靶点之间具有较强结合能力。细胞实验结果显示，环共诺醇可显著抑制SCC-15细胞活力，并呈浓度依赖性，10 μmol/L的环共诺醇处理下的SCC-15细胞存活率显著下降（F=20.15，P<0.001），24 h的IC50为10.14 μmol/L；与Control组相比，环共诺醇高浓度组能显著增加细胞内ROS水平（F=36.13， P<0.001），并促进Cleaved caspase-3表达上调（F= 22.25，P<0.001）。结论：环共诺醇可以抑制OSCC进展，其主要通过调控PI3K/Akt、NF-κB等信号通路，诱导氧化应激并激活凋亡通路发挥作用。
Abstract:
Objective： To predict the potential targets and pathways of Cyclocommunol in the treatment of oral squamous cell car-cinoma （OSCC） based on network pharmacology and molecular docking. Methods： The action targets of Cyclocommunol and OSCC-related disease were comprehensively retrieved using multiple online databases， and the intersecting targets were identified via Venn analysis. A protein-protein interaction （PPI） network of the intersecting targets was constructed， and the key gene modules were identified using Cytoscape soft-ware and the MCODE clustering algorithm. Gene Ontology （GO） functional annotation and Kyoto Ency-clopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed on the screened core targets to reveal the involved biological processes and signaling pathways. Molecular docking analysis was further conducted to evaluate the binding energy and binding modes between Cyclocommunol and the core target proteins， thereby validating its potential activity at the structural level. Mouse head and neck squamous cell carcinoma cells（SCC-15） were selected， and divided into the control group，the low concen-tration of Cyclocommunol group（5 μmol/L）， and the high concentration of Cyclocommunol group（10 μmol/L）. The effects of Cyclocommunol on the biological behavior of SCC-15 cells were assessed through CCK-8， immunofluorescence， and reactive oxygen species （ROS） detection assays. Results： A total of 5 912 OSCC-related targets and 100 Cyclocommunol targets were identified， yielding 81 common intersecting targets through intersection analysis. Based on the MCC algorithm， PPI network analysis identified 10 core targets， including AKT1， ESR1， BCL2， CTNNB1， HSP90AA1， NFKB1， HSP90AB1， BCL2L1， HDAC1， and EP300， which play key regulatory roles in tumor cell proliferation， apoptosis， and inflammatory responses. GO and KEGG enrichment results showed that the potential actions of Cyclocommunol mainly involved key biological processes such as the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） signaling pathway， estrogen signaling pathway， nuclear factor-κB （NF-κB）-related pathways， as well as apoptosis and cell cycle regulation. Molecular docking results further indicated strong binding affinity between Cyclocommunol and these core targets. Cellular experiments revealed that Cyclocommunol significantly inhibited SCC-15 cell viability in a concentration dependent manner. Under treatment with 10 μmol/L Cyclocommunol， the viability of SCC-15 cells was markedly decreased （F=20.15， P<0.001）， with a 24 h IC50 of 10.14 μmol/L. Compared with the control group， the high-concentration Cycloco-mmunol group showed significantly increased intracellular ROS levels （F=36.13， P<0.001） and upregulated the expression of cleaved caspase-3（F=22.25， P<0.001）. Conclusion： Cyclocommunol exerts anti-OSCC effects by regulating signaling pathways such as PI3K/Akt and NF-κB， inducing oxidative stress， and activating the apoptotic pathway.

参考文献/References:

[1] SUNG H， FERLAY J， SIEGEL R L， et al. Global cancer statistics 2020： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin， 2021， 71（3）： 209-249.
[2] SIEGEL R L， MILLER K D， FUCHS H E， et al. Cancer statistics， 2022[J]. CA Cancer J Clin， 2022， 72（1）： 7-33.
[3] VOS J L， ELBERS JBW， KRIJGSMAN O， et al. Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma[J]. Nat Commun， 2021， 12（1）： 7348.
[4] OSAZUWA-PETERS N， SIMPSON M C， ZHAO L， et al. Suicide risk among cancer survivors： head and neck versus other cancers[J]. Cancer， 2018， 124（20）： 4072-4079.
[5] OSAZUWA-PETERS N， ARNOLD L D， LOUX T M， et al. Factors associated with increased risk of suicide among survivors of head and neck cancer： a population-based analysis[J]. Oral Oncol， 2018， 81： 29-34.
[6] LAN W C， TZENG C W， LIN C C， et al. Prenylated flavonoids from Artocarpus altilis： antioxidant activities and inhibitory effects on melanin production [J]. Phytochemistry， 2013， 89： 78-88.
[7] WENG J R， BAI LY， KO H H， et al. Cyclocommunol induces apoptosis in human oral squamous cell carcinoma partially through a Mcl-1-dependent mechanism[J]. Phytomedicine， 2018， 39： 25-32.
[8] ZHOU Y， ZHANG Y， LIAN X， et al. Therapeutic target database update 2022： facilitating drug discovery with enriched comparative data of targeted agents[J]. Nucleic Acids Res， 2022， 50（D1）： D1398-D1407.
[9] GFELLER D， GROSDIDIER A， WIRTH M， et al. SwissTargetPrediction： a web server for target prediction of bioactive small molecules[J]. Nucleic Acids Res， 2014， 42（Web Server issue）： W32-W38.
[10] DAINA A， MICHIELIN O， ZOETE V. SwissTargetPrediction： updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Res， 2019， 47（W1）： W357-W364.
[11] KUKOL A. Consensus virtual screening approaches to predict protein ligands [J]. Eur J Med Chem， 2011， 46（9）： 4661-4664.
[12] KHAN S A， LEE TK W. Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking[J]. Front Pharmacol， 2022， 13： 968148.
[13] CHINN S B， MYERS J N. Oral cavity carcinoma： current management， controversies， and future directions[J]. J Clin Oncol， 2015， 33（29）： 3269-3276.
[14] CHAMOLI A， GOSAVI A S， SHIRWADKAR U P， et al. Overview of oral cavity squamous cell carcinoma： risk factors， mechanisms， and diagnostics[J]. Oral Oncol， 2021， 121： 105451.
[15] HERRMANN J. Adverse cardiac effects of cancer therapies： cardiotoxicity and arrhythmia[J]. Nat Rev Cardiol， 2020， 17（8）： 474-502.
[16] VARRICCHI G， GALDIERO M R， MERCURIO V， et al. Pharmacovigilating cardiotoxicity of immune checkpoint inhibitors[J]. Lancet Oncol， 2018， 19（12）： 1545-1546.
[17] ENGELMAN J A. Targeting PI3K signalling in cancer： opportunities， challenges and limitations[J]. Nat Rev Cancer， 2009， 9（8）： 550-562.
[18] MANNING B D， TALAAYONDIK N. AKT/PKB signaling： navigating the network[J]. Cell， 2017， 169（3）： 381-405.
[19] ROY M， PADMAVATHI G， RAGHUNANDAN B N， et al. Isoform-specific role of Akt in oral squamous cell carcinoma[J]. Biomolecules， 2019， 9（7）： 253.
[20] CHATTOPADHYAY A， CHIANG C W， YANG E. BAD/BCL-xL heterodimerization leads to bypass of G0/G1 arrest[J]. Oncogene， 2001， 20（33）： 4507-4518.
[21] DENG J. How to unleash mitochondrial apoptotic blockades to kill cancers? [J]. Acta Pharm Sin B， 2017， 7（1）： 18-26.
[22] DAVIDS M S， LETAI A. Targeting the B-cell lymphoma/leukemia 2 family in cancer[J]. J Clin Oncol， 2012， 30（25）： 3127-3135.
[23] KALONI D， DIEPSTRATEN S T， STRASSER A， et al. BCL-2 protein family： attractive targets for cancer therapy[J]. Apoptosis， 2023， 28（1-2）： 20-38.
[24] TANIGUCHI K， KARIN M. NF-κB， inflammation， immunity and cancer： coming of age[J]. Nat Rev Immunol， 2018， 18（5）： 309-324.
[25] YU H， LIN L， ZHANG Z， et al. Targeting NF-κB pathway for the therapy of diseases： mechanism and clinical study[J]. Signal Transduct Target Ther， 2020， 5（1）： 209.
[26] 严明， 陈万涛. NF-κB信号转导通路和肿瘤发生、转移关系的研究进展[J]. 北京口腔医学， 2007（1）： 53-55.
[27] JOHNSON J， SHI Z， LIU Y， et al. Inhibitors of NF-kappa B reverse cellular invasion and target gene upregulation in an experimental model of aggressive oral squamous cell carcinoma[J]. Oral Oncol， 2014， 50（5）： 468-477.
[28] VANDER BROEK R， SNOW G E， CHEN Z， et al. Chemoprevention of head and neck squamous cell carcinoma through inhibition of NF-κB signaling [J]. Oral Oncol， 2014， 50（10）： 930-941.
[29] WHITESELL L， LINDQUIST S L. HSP90 and the chaperoning of cancer [J]. Nat Rev Cancer， 2005， 5（10）： 761-772.
[30] SCHOPF F H， BIEBL M M， BUCHNER J. The HSP90 chaperone machinery [J]. Nat Rev Mol Cell Biol， 2017， 18（6）： 345-360.
[31] FAN G， TU Y， WU N， et al. The expression profiles and prognostic values of HSPs family members in head and neck cancer[J]. Cancer Cell Int， 2020， 20（1）： 220.

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备注/Memo

备注/Memo:
（2025-11-21收稿）
作者简介 时伟峰（1996-），男，博士在读，研究方向：头颈肿瘤、免疫治疗、纳米材料应用；通信作者：吴延升，E-mail：yansheng1981@163.com。
更新日期/Last Update: 2026-07-15