基于网络药理学和实验验证探究鲍式层孔菌多酚的抗头颈鳞癌机制

doi:10.11958/20250580

天津医药 ›› 2025, Vol. 53 ›› Issue (5): 456-461.doi: 10.11958/20250580

基于网络药理学和实验验证探究鲍式层孔菌多酚的抗头颈鳞癌机制

余朝霞¹(), 马贲¹, 邱林², 高倩², 尼娜³^,^△()

1 天津市天津医院口腔科（邮编300211）
2 北京大学口腔医院中心实验室
3 天津市口腔医院，南开大学口腔医院牙体牙髓病学一科

收稿日期:2025-02-14 修回日期:2025-03-15 出版日期:2025-05-15 发布日期:2025-05-28
通讯作者: △ E-mail：nina_tj@163.com
作者简介:余朝霞（1995），女，住院医师，主要从事头颈部鳞癌新型化疗药物开发研究。E-mail：863061218@qq.com
基金资助:
天津市科技计划项目(22JCYBJC01170)

Elucidation of the anti-head and neck squamous cell carcinoma mechanism of Phellinus baumii polyphenol based on network pharmacology and experimental verification

YU Zhaoxia¹(), MA Ben¹, QIU Lin², GAO Qian², NI Na³^,^△()

1 Department of Stomatology, Tianjin Hospital, Tianjin 300211, China
2 Central Laboratory, Peking University School and Hospital of Stomatology
3 Department I of Endodontics, Tianjin Stomatological Hospital, Nankai University Stomatology Hospital

Received:2025-02-14 Revised:2025-03-15 Published:2025-05-15 Online:2025-05-28
Contact: △ E-mail：nina_tj@163.com

余朝霞, 马贲, 邱林, 高倩, 尼娜. 基于网络药理学和实验验证探究鲍式层孔菌多酚的抗头颈鳞癌机制[J]. 天津医药, 2025, 53(5): 456-461.

YU Zhaoxia, MA Ben, QIU Lin, GAO Qian, NI Na. Elucidation of the anti-head and neck squamous cell carcinoma mechanism of Phellinus baumii polyphenol based on network pharmacology and experimental verification[J]. Tianjin Medical Journal, 2025, 53(5): 456-461.

摘要/Abstract

摘要：

目的基于网络药理学和体外实验探究鲍式层孔菌多酚（PBP）作用于头颈部鳞状细胞癌（HNSCC）的靶点并分析潜在机制。方法分别通过中药系统药理学数据库与分析平台（TCMSP）、药物数据库（DrugBank）、基因数据库（GeneCards）、比较毒理基因组学数据库（CTD）和人类孟德尔遗传病数据库（OMIM）筛选PBP的有效成分以及PBP作用于HNSCC的潜在靶点；使用String数据库构建潜在靶点互作网络，并进行两步拓扑分析筛选核心靶点；使用注释、可视化和集成发现数据库对潜在靶点进行富集分析。体外培养人HNSCC细胞系SCC-15和SCC-25，分别采用0、25、50 mg/L PBP干预，通过细胞增殖及毒性检测（CCK-8）、集落形成实验检测细胞的增殖和集落形成能力，Western blot实验检测2种细胞中PBP核心靶点蛋白的表达。结果 PBP的17种有效成分共得到280个靶点，其中有264个是HNSCC相关基因；两步拓扑结构分析得到缺氧诱导因子1A（HIF1A）、肿瘤抑癌基因p53（TP53）、丝氨酸/苏氨酸蛋白激酶1（AKT1）、信号转导和转录激活因子3（STAT3）、细胞周期蛋白A2（CCNA2）和Jun原癌基因（JUN）6个核心靶点；富集结果提示PBP可能通过多种通路在HNSCC中发挥作用。体外实验结果显示，随着PBP干预浓度的升高，SCC-15和SCC-25细胞增殖能力和集落形成能力明显下降（P<0.05），同时STAT3、AKT1和CCNA2的蛋白表达水平降低（P<0.05）。结论 PBP能够多靶点、多途径地抑制HNSCC的增殖。

关键词: 头颈部肿瘤, 真菌, 基因调控网络, 细胞增殖, 鲍式层孔菌多酚

Abstract:

Objective To investigate the effects of Phellinus baumii polyphenol (PBP) on head and neck squamous cell carcinoma (HNSCC) and analyze the potential mechanism based on network pharmacology and in vitro experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), DrugBank, GeneCards, Comparative Toxicogenomics Database (CTD) and Online Mendelian Inheritance in Man (OMIM) database were used to screen the active components of PBP and potential targets of PBP on HNSCC. The potential target interaction network was constructed using String database, and the core targets were screened by two-step topology analysis. Enrichment analysis of potential targets was performed using the DAVID database. Human HNSCC cell lines SCC-15 and SCC-25 were cultured in vitro using PBP intervention of 0, 25, 50 mg/L, respectively. The cell proliferation and colony formation ability were detected by cell counting reagent (CCK-8) and colony formation assay. Western blot assay was used to detect the expression of PBP core target protein in 2 cell lines. Results A total of 280 targets were identified for 17 active components of PBP, 264 of which were HNSCC-related genes. Two-step topology analysis showed that hypoxia inducible factor 1 subunit alpha (HIF1A), tumor protein p53 (TP53), AKT serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), cyclin A2 (CCNA2) and JUN proto-oncogene (JUN) were the core targets. The enrichment results suggested that PBP may play a role in HNSCC through various pathways. In vitro experiment results showed that with the increase of PBP intervention concentration, the proliferation ability and colony formation ability of SCC-15 and SCC-25 cells were significantly decreased (P<0.05), while the protein expression levels of STAT3, AKT1 and CCNA2 were decreased (P<0.05). Conclusion PBP can inhibit the progression of HNSCC by multi-target and multi-pathway.

Key words: head and neck neoplasms, fungi, gene regulatory networks, cell proliferation, P. baumii polyphenol

中图分类号:

R739.81

图/表 8

图1 PBP作用于HNSCC的潜在靶点分析图 A：PBP有效成分靶点合并花瓣图；B：HNSCC相关基因韦恩图；C：PBP有效成分靶点与HNSCC基因韦恩图。

Fig.1 Potential target analysis of PBP on HNSCC

图2 两步拓扑结构分析PBP作用于HNSCC的核心靶点

Fig.2 Two-step topology analysis of the core targets of PBP in HNSCC

图3 PBP作用于HNSCC潜在靶点的KEGG富集分析

Fig.3 KEGG enrichment analysis of potential targets of PBP on HNSCC

图4 不同浓度PBP干预后SCC-15和SCC-25细胞增殖曲线 SCC-15细胞：F24 h=71.637，F48 h =293.795，F72 h =962.000，均P<0.01；SCC-25细胞：F24 h=57.372，F48 h =285.875，F72 h =655.359，均P<0.01；组间比较：a与0 mg/L PBP组比较，b与25 mg/L PBP组比较，P<0.05。

Fig.4 Proliferation curves of SCC-15 and SCC-25 cells after intervention with different concentrations of PBP

图5 不同浓度PBP对SCC-15和SCC-25集落形成能力的影响

Fig. 5 Effects of different concentrations of PBP on colony formation capacity of SCC-15 and SCC-25 cells

表1 各组细胞集落形成数量比较（n=3,$\bar{x}±s$）

Tab.1 Comparison of the number of cell colonies between three groups

组别	SCC-15集落数/个	SCC-25集落数/个
0 mg/L PBP组	115.67±6.03	63.33±7.63
25 mg/L PBP组	90.33±9.00^a	37.67±2.52^a
50 mg/L PBP组	55.67±4.04^ab	22.33±2.52^ab
F	61.393^＊＊	54.399^＊＊

图6 PBP对SCC-15和SCC-25细胞STAT3、AKT1和CCNA2蛋白表达的影响 1 ：SCC-15细胞0 mg/L PBP组；2：SCC-15细胞50 mg/L PBP组；3：SCC-25细胞0 mg/L组 PBP组；4：SCC-25细胞50 mg/L PBP组。

Fig. 6 Effect of PBP on STAT3, AKT1 and CCNA2 protein expression in SCC-15 and SCC-25 cells

表2 各组细胞蛋白表达水平比较（n=3,$\bar{x}±s$）各组细胞蛋白表达水平比较（n=3,$\bar{x}±s$）

Tab.2 Comparison of cell protein levels between two groups

组别	SCC-15
组别	STAT3	AKT1	CCNA2
0 mg/L PBP组	1.00±0.02	1.00±0.04	1.00±0.01
50 mg/L PBP组	0.55±0.08	0.69±0.05	0.38±0.06
t	8.873^＊＊	7.783^＊＊	16.231^＊＊
组别	SCC-25
组别	STAT3	AKT1	CCNA2
0 mg/L PBP组	1.00±0.04	1.00±0.01	1.00±0.01
50 mg/L PBP组	0.77±0.01	0.39±0.06	0.52±0.05
t	8.304^＊＊	15.550^＊＊	13.705^＊＊

参考文献 21

[1]	BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263. doi:10.3322/caac.21834.
[2]	ORTIZ-CUARAN S, BOUAOUD J, KARABAJAKIAN A, et al. Precision medicine approaches to overcome resistance to therapy in head and neck cancers[J]. Front Oncol, 2021, 11:614332. doi:10.3389/fonc.2021.614332.
[3]	CHEN W, TAN H, LIU Q, et al. A review:the bioactivities and pharmacological applications of phellinus linteus[J]. Molecules, 2019, 24(10):1888. doi:10.3390/molecules24101888.
[4]	ESMEETA A, ADHIKARY S, DHARSHNAA V, et al. Plant-derived bioactive compounds in colon cancer treatment:an updated review[J]. Biomed Pharmacother, 2022, 153:113384. doi:10.1016/j.biopha.2022.113384.
[5]	YANG W E, CHEN Y T, SU C W, et al. Hispolon induces apoptosis in oral squamous cell carcinoma cells through JNK/HO-1 pathway activation[J]. J Cell Mol Med, 2023, 27(9):1250-1260. doi:10.1111/jcmm.17729.
[6]	LIU X, CUI S, DAN C, et al. Phellinus baumii Polyphenol:a potential therapeutic candidate against lung cancer cells[J]. Int J Mol Sci, 2022, 23(24):16141. doi:10.3390/ijms232416141.
[7]	LI Q, TIE Y, ALU A, et al. Targeted therapy for head and neck cancer:signaling pathways and clinical studies[J]. Signal Transduct Target Ther, 2023, 8(1):31. doi:10.1038/s41392-022-01297-0.
[8]	WANG Y J, HAO Y Y, LEE D H, et al. Hispidin increases cell apoptosis and ferroptosis in prostate cancer cells through phosphatidylinositol-3-kinase and mitogen-activated protein kinase signaling pathway[J]. Anticancer Res, 2024, 44(6):2533-2544. doi:10.21873/anticanres.17059.
[9]	BENAROUS K, SERSEG T, MERMER A, et al. Exploring the anti-cancer potential of hispidin:a comprehensive in silico and in vitro study on human osteosarcoma Saos2 cells[J]. Chem Biodivers, 2024, 21(5):e202301833. doi:10.1002/cbdv.202301833.
[10]	CARMELIET P, DOR Y, HERBERT J M, et al. Role of HIF-1alpha in hypoxia-mediated apoptosis,cell proliferation and tumour angiogenesis[J]. Nature, 1998, 394(6692):485-490. doi:10.1038/28867.
[11]	YANG Z, SU W, WEI X, et al. HIF-1α drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1[J]. Cell Rep, 2023, 42(8):112945. doi:10.1016/j.celrep.2023.112945.
[12]	SACCONI A, MUTI P, PULITO C, et al. Immunosignatures associated with TP53 status and co-mutations classify prognostically head and neck cancer patients[J]. Mol Cancer, 2023, 22(1):192. doi:10.1186/s12943-023-01905-9.
[13]	NATHAN C A, KHANDELWAL A R, WOLF G T, et al. TP53 mutations in head and neck cancer[J]. Mol Carcinog, 2022, 61(4):385-391. doi:10.1002/mc.23385.
[14]	GIRI R, HOTA S K, SENAPATI U. Expression of TP53 in oral squamous cell carcinoma and its correlation with adverse histopathological features[J]. J Cancer Res Ther, 2023, 19(2):278-282. doi:10.4103/jcrt.jcrt_1963_21.
[15]	SUN E C, DONG S S, LI Z J, et al. Clinicopathological significance of AKT1 and PLK1 expression in oral squamous cell carcinoma[J]. Dis Markers, 2022, 2022:7300593. doi:10.1155/2022/7300593.
[16]	SHARIF SIAM M K, SARKER A, SAYEEM M. In silico drug design and molecular docking studies targeting Akt1(RAC-alpha serine/threonine-protein kinase)and Akt2 (RAC-beta serine/threonine-protein kinase) proteins and investigation of CYP (cytochrome P450) inhibitors against MAOB (monoamine oxidase B)for OSCC(oral squamous cell carcinoma)treatment[J]. J Biomol Struct Dyn, 2021, 39(17):6467-6479. doi:10.1080/07391102.2020.1802335.
[17]	BICKETT T E, KNITZ M W, PIPER M, et al. Dichotomous effects of cellular expression of STAT3 on tumor growth of HNSCC[J]. Mol Ther, 2022, 30(3):1149-1162. doi:10.1016/j.ymthe.2021.11.011.
[18]	马佳佳, 张亚苹, 杨斌, 等. ATOX1通过JAK2/STAT3通路促进肝癌细胞生物学行为的机制探讨[J]. 天津医药, 2024, 52(9):907-912.
	MA J J, ZHANG Y P, YANG B, et al. Mechanism study of ATOX1 promoting biological behavior of hepatocellular carcinoma cells through JAK2/STAT3 pathway[J]. Tianjin Med J, 2024, 52(9):907-912. doi:10.11958/20240221.
[19]	HUANG Q, YE M, LI F, et al. Prognostic and clinicopathological significance of transcription factor c-Jun in hypopharyngeal squamous cell carcinoma:a 3-year follow-up retrospective study[J]. BMC Cancer, 2022, 22(1):1019. doi:10.1186/s12885-022-10113-5.
[20]	MASTRONIKOLIS N, CHRYSOVERGIS A, PAPANIKOLAOU V, et al. C-Jun transcription factor oncogenic activation in oral carcinoma[J]. Maedica (Bucur), 2024, 19(2):350-354. doi:10.26574/maedica.2024.19.2.3502024.
[21]	MUSGROVE E A, CALDON C E, BARRACLOUGH J, et al. Cyclin D as a therapeutic target in cancer[J]. Nat Rev Cancer, 2011, 11(8):558-572. doi:10.1038/nrc3090.

基于网络药理学和实验验证探究鲍式层孔菌多酚的抗头颈鳞癌机制

Elucidation of the anti-head and neck squamous cell carcinoma mechanism of Phellinus baumii polyphenol based on network pharmacology and experimental verification

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