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

卷:

31卷

期数:

2025年06期

页码:

514-520

栏目:

肿瘤疾病专题

出版日期:

2025-11-20

文章信息/Info

Title:

Mechanistic investigation of palmitic acid against prostate cancer based on network pharmacology and molecular docking

文章编号:

1006-8147(2025)06-0514-07

作者:

王培钰; 杨絮婷; 庞瑞康; 孔德新; 王 冉

（天津医科大学药学院临床药学系，天津 300070）

Author(s):

WANG Peiyu;  YANG Xuting;  PANG Ruikang;  KONG Dexin;  WANG Ran

（Department of Clinical Pharmacy， School of Pharmacy， Tianjin Medical University， Tianjin 300070， China）

关键词:

棕榈酸; 前列腺癌; 网络药理学; 分子对接

Keywords:

palmitic acid;  prostate cancer;  network pharmacology;  molecular docking

分类号:

R737.25

DOI:

10.20135/j.issn.1006-8147.2025.06.0514

文献标志码:

A

摘要:

目的：基于网络药理学与分子对接技术探讨棕榈酸抗前列腺癌的潜在分子靶点及作用机制。方法：利用SwissTargetPrediction平台、Pharmmapper和Comparative Toxicogenomics Database获取天然产物棕榈酸的靶点；利用GeneCards和OMIM数据库获取前列腺癌治疗的靶点基因；使用Venny软件获得棕榈酸-前列腺癌交集靶点；借助STRING平台构建棕榈酸抗前列腺癌靶点的蛋白质相互作用（PPI）网络模型；运用Cytoscape 3.10.2筛选核心靶点；采用微生信数据平台进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）富集分析；使用Autodock软件对棕榈酸与核心靶点的相互作用进行分子对接验证。结果：共获得352个棕榈酸-前列腺癌交集靶点，其中47个为核心靶点。GO功能富集分析提示基因功能主要涉及对多种刺激的应答反应。KEGG通路富集分析提示棕榈酸抗前列腺癌的作用机制可能与晚期糖基化终末产物 - 晚期糖基化终末产物受体（AGE-RAGE）和肿瘤坏死因子（TNF）信号通路等密切相关。分子对接结果表明棕榈酸与热休克蛋白90α家族A类成员1（HSP90AA1）、肿瘤蛋白p53（TP53）、原癌基因酪氨酸蛋白激酶Src （SRC）、雌激素受体1（ESR1）、转录因子AP-1（JUN）和转录因子p65（RELA）等靶点具有较高的结合活性。结论：棕榈酸通过作用于多个靶点并调控多条信号通路发挥抗前列腺癌的作用，其中TP53和SRC靶点以及AGE-RAGE和TNF通路可能是研究棕榈酸抗前列腺癌机制的重点。

Abstract:

Objective： To explore the potential molecular targets and the mechanisms of palmitic acid against prostate cancer by network pharmacology and molecular docking. Methods： The targets of natural product palmitic acid were obtained from SwissTargetPrediction platform， Pharmmapper， and the Comparative Toxicogenomics Database. Primary targets for prostate cancer treatment were collected from GeneCards and OMIM databases. The intersection targets of palmitic acid against prostate cancer was determined using Venny software. A protein-protein interaction （PPI） network model of palmitic acid against prostate cancer target was constructed via the STRING platform， and core targets were identified using Cytoscape 3.10.2. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were conducted through a microbiology data platform. Finally， molecular docking was performed using AutoDock software to validate the interactions between palmitic acid and the core targets. Results： A total of 352 intersection targets between palmitic acid and prostate cancer were identified， among which 47 were recognized as core targets. GO functional enrichment analysis indicated that gene functions were primarily involved in responses to various stimuli. KEGG pathway enrichment analysis suggested that the mechanism of palmitic acid against prostate cancer might be closely associated with the advanced glycation end products-receptor for advanced glycation end products （AGE-RAGE） and tumor necrosis factor （TNF） signaling pathway. Molecular docking analysis further revealed that palmitic acid exhibited high binding affinity with key targets， including heat shock protein 90α family class A member 1 （HSP90AA1）， tumor protein p53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）， estrogen receptor 1 （ESR1）， transcription factor AP-1 （JUN） and transcription factor p65 （RELA）. Conclusion： Palmitic acid exerts anticancer effects against prostate cancer through acting on multiple targets and regulating signaling pathways. Among these， TP53 and SRC targets， as well as the AGE-RAGE and TNF signaling pathways， appear to play pivotal roles in the mechanism of palmitic acid against prostate cancer.

参考文献/References:

[1] 姚一菲，孙可欣，郑荣寿. 《2022全球癌症统计报告》解读：中国与全球对比[J]. 中国普外基础与临床杂志， 2024， 31（7）：769-780.
[2] 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.
[3] LIU J， DONG L， ZHU Y， et al. Prostate cancer treatment-China’s perspective[J]. Cancer Lett， 2022， 550：215927.
[4] 张威.基于糖代谢标记靶向前列腺癌纳米材料的合成与抗肿瘤活性研究[D].河南大学， 2024.
[5] CARTA G， MURRU E， BANNI S， et al. Palmitic acid： physiological role， metabolism and nutritional implications[J]. Front Physiol， 2017， 8：902.
[6] ZHU Z， FENG S， ZENG A， et al. Advances in palmitoylation： a key regulator of liver cancer development and therapeutic targets[J]. Biochem Pharmacol， 2025， 234：116810.
[7] HSIAO Y H， LIN C I， LIAO H， et al. Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells[J]. Int J Mol Sci， 2014， 15（11）：20876–20899.
[8] PEREIRA D M， CORREIA-DA-SILVA G， VALENTAO P， et al. Palmitic acid and ergosta-7，22-dien-3-ol contribute to the apoptotic effect and cell cycle arrest of an extract from marthasterias glacialis L. in neuroblastoma cells[J]. Mar Drugs， 2013， 12（1）：54-68.
[9] ZHU S， JIAO W， XU Y， et al. Palmitic acid inhibits prostate cancer cell proliferation and metastasis by suppressing the PI3K/Akt pathway[J]. Life Sci， 2021， 286：120046.
[10] BAUMANN J， WONG J， SUN Y， et al. Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells[J]. BMC Cancer， 2016， 16：551.
[11] HE Y， REZAEI S， JUNIOR RFA， et al. Multifunctional role of lipids in modulating the tumorigenic properties of 4T1 breast cancer cells[J]. Int J Mol Sci， 2022， 23（8）：4240.
[12] KUANG H， SUN X， LIU Y， et al. Palmitic acid-induced ferroptosis via CD36 activates ER stress to break calcium-iron balance in colon cancer cells[J]. FEBS J， 2023， 290（14）：3664-3687.
[13] ARINDAM S， DIPSHIKHA K， THIRUKUMARAN K， et al. Apigenin exerts anti-cancer effects in colon cancer by targeting HSP90AA1[J]. J Biomol Struct Dyn， 2025， 43（7）：3557-3569.
[14] LIU S， XU Y， YAO X， et al. Perillaldehyde ameliorates sepsis-associated acute kidney injury via inhibiting HSP90AA1-mediated ferroptosis and pyroptosis： molecular structure and protein interaction of HSP90AA1[J]. Int J Biol Macromol， 2025， 304（P2）： 140954-140954.
[15] TRIGIANTE G， LU X. ASPP [corrected] and cancer[J]. Nat Rev Cancer， 2006， 6（3）：217-226.
[16] AUBREY B J， STRASSER A， KELLY G L. Tumor-suppressor functions of the TP53 pathway[J]. Cold Spring Harb Perspect Med， 2016， 6（5）：a026062.
[17] AMARAL J D， XAVIER J M， STEER C J， et al. The role of p53 in apoptosis[J]. Discov Med， 2010， 9（45）：145-152.
[18] JIANG L， KON N， LI T， et al. Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature， 2015， 520（7545）：57-62.
[19] SU Y， ZHU K， WANG J， et al. Advancing Src kinase inhibition： from structural design to therapeutic innovation-a comprehensive review[J]. Eur J Med Chem， 2025， 287：117369-117369.
[20] LOPEZ M， SPEHNER L， ANDRE F， et al. Exploring the role of ESR1 mutations in metastatic hormone receptor-positive breast cancer T cell immune surveillance disruption[J]. Breast Cancer Res， 2025， 27（1）： 19.
[21] PAICHADZE A A， CHASHNIKOVA E P， GOLUBEVA S A. The role of ESR1 gene mutation in therapy selection for HR+/HER2- metastatic breast cancer： a review[J]. J Mod Oncol， 2025， 26（4）： 410-413.
[22] 范潇龙，侯秋霞，罗桃红，等. Jun转录因子家族与肝细胞癌的研究进展[J]. 中国医药科学，2023，13（5）：49-52.
[23] PANWALKAR A， VERSTOVSEK S， GILES F. Nuclear factor-kappaB modulation as a therapeutic approach in hematologic malignancies[J]. Cancer， 2004， 100（8）：1578-1589.
[24] WU L， JIN Y， ZHAO X， et al. Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α[J]. Cell Metab， 2023， 35（9）：1580-1596.
[25] JING Y， SUN K， LIU W， et al. Tumor necrosis factor-α promotes hepatocellular carcinogenesis through the activation of hepatic progenitor cells[J]. Cancer Lett， 2018， 434：22-32.
[26] WAGHELA B N， VAIDYA F U， RANJAN K， et al. AGE-RAGE synergy influences programmed cell death signaling to promote cancer[J]. Mol Cell Biochem， 2021， 476（2）：585-598.
[27] 包继明. AGE-RAGE激活PI3K/Akt通路调控视网膜母细胞瘤蛋白促进前列腺癌细胞增殖的机制研究[D]. 南方医科大学， 2014.
[28] ASTANEHE A， ARENILLAS D， WASSERMAN W W， et al. Mecha-nisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer[J]. J Cell Sci， 2008， 121（Pt 5）：664-674.
[29] LU Y， YU Q， LIU J H， et al. Src family protein-tyrosine kinases alter the function of PTEN to regulate phosphatidylinositol 3-kinase/AKT cascades[J]. J Biol Chem， 2003， 278（41）：40057-40066.
[30] YAMAKI H， NAKAJIMA M， SHIMOTOHNO K W， et al. Molecular basis for the actions of Hsp90 inhibitors and cancer therapy[J]. J Antibiot （Tokyo）， 2011， 64（9）：635-644.
[31] JANG S Y， JANG S W， KO J. Celastrol inhibits the growth of estrogen positive human breast cancer cells through modulation of estrogen receptor α[J]. Cancer Lett， 2011， 300（1）：57-65.
[32] WISDOM R， JOHNSON R S， MOORE C. c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms[J]. EMBO J， 1999， 18（1）：188-197.
[33] PERKINS N D， FELZIEN L K， BETTS J C， et al. Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator[J]. Science， 1997， 275（5299）：523-527.
[34] CARTA G， MURRU E， BANNI S， et al. Palmitic acid： physiological role， metabolism and nutritional Implications[J]. Front Physiol， 2017， 8：902.

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备注/Memo

备注/Memo:

作者简介 王培钰（2000-），女，硕士在读，研究方向：药理学；通信作者：王冉，E-mail：wangran@tmu.edu.cn；孔德新，E-mail： kongdexin@tmu.edu.cn。

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更新日期/Last Update: 2025-11-20