基于网络药理学及分子对接技术探讨夏枯草治疗甲状腺癌的作用机制

doi:10.3969/j.issn.1009-976X.2020.05.005

摘要/Abstract

摘要： 目的运用网络药理学联合分子对接技术分析夏枯草治疗甲状腺癌的分子机制。方法利用TCMSP数据库预测夏枯草的主要活性成分,并用TCMSP和PubChem数据库获取所有活性成分对应靶点;通过GeneCards及OMIM数据库收集甲状腺治疗甲状腺癌的靶点。利用STRING数据库获取蛋白间的相互作用信息,并通过R语言进行拓扑学分析及可视化。利用R包clusterProfiler对上述取得的药物和疾病的交集靶点进行GO和KEGG pathway分析。利用Cytoscape 3.7.2构建活性成分-靶点-疾病网络,并进行拓扑学分析,得到核心化合物,用分子对接对核心靶点和化合物进行验证。结果槲皮素、木犀草素、山奈酚、谷甾醇可能是夏枯草治疗甲状腺癌的核心成分,AKTI、VEGFA、CASP3、MYC、JUN、MAPK8、IL6、EGFR、MAPK1、EGF可能是治疗的重要靶点。结论夏枯草治疗甲状腺癌体现了多成分、多靶点、多通路的特点,为夏枯草有效成分的筛选及进一步研究提供了理论基础。

关键词: 网络药理学, 甲状腺癌, 分子对接, 作用机制, 夏枯草

Abstract: Objective To analyze the molecular mechanism of Prunella vulgaris in the treatment of thyroid cancer using network pharmacology combined with molecular docking technology. Methods TCMSP database was used to predict the main active components of Prunella vulgaris, and TCMSP and PubChem database were used to obtain the corresponding targets of all active components. Thyroid targets for the treatment of thyroid cancer were collected through GeneCards and OMIM database. The interaction information between proteins was obtained by using STRING database, and the topology analysis and visualization were carried out by using R language. GO and KEGG pathway analysis was conducted on the intersection targets of drugs and diseases obtained above using the clusterProfiler. Cytoscape 3.7.2 was used to construct the active component-target-disease network, and the core compounds were obtained through topological analysis. The core targets and compounds were verified by molecular docking. Results Quercetin, luteolin, kaempferol and sitosterol may be the core components in the treatment of thyroid cancer, while AKTI, VEGFA, CASP3, MYC, JUN, MAPK8, IL6, EGFR, MAPK1 and EGF may be the important therapeutic targets. Conclusion The treatment of thyroid carcinoma by Prunella vulgaris shows the characteristics of multiple components, multiple targets and multiple pathways, which provides a theoretical basis for the screening and further study of the effective components of Prunella vulgaris.

Key words: thyroid carcinoma, Prunella vulgaris, network pharmacology, molecular docking, mechanism

中图分类号:

R736.1

涂星强, 张晶晶, 彭小彬, 杜国能, 许礼笑子, 许永辉, 肖玉根. 基于网络药理学及分子对接技术探讨夏枯草治疗甲状腺癌的作用机制[J]. 岭南现代临床外科, 2020, 20(05): 567-572.

TU Xing-qiang, ZHANG Jing-jing, PENG Xiao-bin, DU Guo-neng, XULI Xiao-zi, XU Yong-hui, XIAO Yu-gen. Study of mechanism of Prunella vulgaris decoction on thyroid cancer based on network pharmacology and molecular docking technology[J]. Lingnan Modern Clinics in Surgery, 2020, 20(05): 567-572.

参考文献

[1] Fazal H, Abbasi BH, Ahmad N, Ali M.Elicitation of Medicinally Important Antioxidant Secondary Metabolites with Silver and Gold Nanoparticles in Callus Cultures of Prunella vulgaris L[J]. Appl Biochem Biotechnol, 2016, 180(6):1076-1092.
[2] Yu Q, Qi J, Wang L, et al.Pentacyclic triterpenoids from spikes of Prunella vulgaris L. inhibit glycogen phosphorylase and improve insulin sensitivity in 3T3-L1 adipocytes[J]. Phytother Res, 2015, 29(1): 73-79.
[3] Psotová J, Kolár M, Sousek J, et al.Biological activities of Prunella vulgaris extract[J]. Phytother Res, 2003, 17(9): 1082-1087.
[4] Du D, Lu Y, Cheng Z, Chen D.Structure characterization of two novel polysaccharides isolated from the spikes of Prunella vulgaris and their anticomplement activities[J]. J Ethnopharmacol, 2016, 193: 345-353.
[5] 翟欣, 奚梦倩, 郭巧生, 等. 夏枯草中苦味物质的初步分析[J]. 中国中草药杂志, 2014, 39(3): 423-426.
[6] Su YC, Lin IH, Siao YM, et al.Modulation of the Tumor Metastatic Microenvironment and Multiple Signal Pathways by Prunella vulgaris in Human Hepatocellular Carcinoma[J]. Am J Chin Med, 2016, 44(4):835-849.
[7] Hwang YJ, Lee EJ, Kim HR, Hwang KA.NF-κB-targeted anti-inflammatory activity of Prunella vulgaris var. lilacina in macrophages RAW 264.7[J]. Int J Mol Sci, 2013, 14(11):21489-21503.
[8] Tan J, Qi H, Ni J.Extracts of endophytic fungus xkc-s03 fromPrunella vulgaris L. spica inhibit gastric cancerin vitroandin vivo[J]. Oncol Lett, 2015, 9(2):945-949.
[9] Kim HI, Quan FS, Kim JE, et al.Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina[J]. Biochem Biophys Res Commun, 2014, 451(2):282-287.
[10] Hao J, Ding XL, Yang X, Wu XZ.Prunella vulgaris Polysaccharide Inhibits Growth and Migration of Breast Carcinoma-Associated Fibroblasts by Suppressing Expression of Basic Fibroblast Growth Factor[J]. Chin J Integr Med, 2020, 26(4):270-276.
[11] 熊燚,赵敏,谭剑斌,等. 夏枯草对人甲状腺髓样癌细胞增殖的影响和诱导其凋亡的作用机制[J]. 中华中医药杂志,2018, 33(8):3379-3384.
[12] Bai Y, Xia B, Xie W, et al.Phytochemistry and pharmacological activities of the genus Prunella[J]. Food Chem,2016,204:483-496.
[13] Quagliariello V, Armenia E, Aurilio C, et al.New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase[J]. J Cell Physiol,2016,231(8):1784-1795.
[14] Yin F, Giuliano AE, Van Herle AJ.Growth inhibitory effects of flavonoids in human thyroid cancer cell lines[J]. Thyroid,1999,9(4):369-376.
[15] Wang X, Li M, Hu M, et al.BAMBI overexpression together with beta-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-beta/Smad2/3 pathway[J]. Oncol Rep,2017,37(5):3046-3054.
[16] Wang B, Zhao CH, Sun G, et al.IL-17 induces the proliferation and migration of glioma cells through the activation of PI3K/Akt1/NF-kappaB-p65[J]. Cancer Lett,2019,447:93-104.
[17] Zhao X, Wang T, Cai B, et al.MicroRNA-495 enhances chondrocyte apoptosis, senescence and promotes the progression of osteoarthritis by targeting AKT1[J]. Am J Transl Res,2019,11(4):2232-2244.
[18] Fukumura D, Kloepper J, Amoozgar Z, et al.Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges[J]. Nat Rev Clin Oncol,2018,15(5):325-340.
[19] Hu F, Li H, Liu L, et al.Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1beta/VEGFA signalling[J]. Mol Cancer,2018,17(1):107.
[20] Hill RM, Kuijper S, Lindsey JC, et al.Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease[J]. Cancer Cell,2015,27(1):72-84.
[21] Albihn A, Johnsen JI, Henriksson MA.MYC in oncogenesis and as a target for cancer therapies[J]. Adv Cancer Res,2010,107:163-224.
[22] Kawasaki T, Kawai T.Toll-like receptor signaling pathways[J]. Front Immunol,2014,5:461.
[23] Chen CY, Kao CL, Liu CM. The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway[J]. Int J Mol Sci,2018,19(9): 2729.
[24] Yang S, Wang J, Brand DD, et al.Role of TNF-TNF Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications[J]. Front Immunol,2018,9:784.
[25] Martini M, De Santis MC, Braccini L, et al.PI3K/AKT signaling pathway and cancer: an updated review[J]. Ann Med,2014,46(6):372-383.
[26] Aubrey BJ, Kelly GL, Janic A, et al.How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?[J]. Cell Death Differ,2018,25(1):104-113.