全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

基于网络药理学和分子对接技术分析茵陈治疗肝癌的潜在作用机制
Analysis of the Potential Mechanism of Artemisiae Scopariae Herba in the Treatment of Liver Cancer based on Network Pharmacology and Molecular Docking Technology

DOI: 10.12677/HJBM.2021.114026, PP. 201-213

Keywords: 茵陈,肝癌,网络药理学,分子对接
Artemisiae Scopariae Herba
, Liver Cancer, Network Pharmacology, Molecular Docking

Full-Text   Cite this paper   Add to My Lib

Abstract:

目的:运用网络药理学和分子对接技术阐释茵陈抗肝癌的作用机制。方法:用TCMSP和UniProt数据库收集茵陈的活性成分并预测其潜在靶点。通过GeneCards、OMIM、TTD数据库筛选肝癌相关靶点。用在线软件Draw Venn Diagram将药物和疾病靶点取交集,将交集靶点导入DAVID 6.8在线数据库进行GO和KEGG分析。通过STRING数据库构建靶蛋白互作网络,用Cytoscape软件筛选关键基因,并用AutoDock Vina软件对关键靶点进行分子对接分析。结果:茵陈共筛选出13个活性成分,药物和疾病交集靶点103个,最终筛选出CDKN1A、CDK2、JUN、E2F1、RB1、TNF、IL6、CCNA2、IL1B、CXCL8 10个关键靶点,关键靶点与部分活性成分对接较好。结论:茵陈中的活性成分通过作用于CDKN1A、CDK2、CXCL8等靶点,参与调控细胞周期、机体的炎症反应以及癌症等信号通路,从而可能发挥对肝癌的治疗作用。
Objective: The network pharmacology and molecular docking technology were used to elucidate the mechanism of Artemisiae Scopariae Herba (ASH) against liver cancer. Methods: TCMSP and UniProt databases were used to collect the active components of ASH and predict their potential targets. The target of liver cancer was screened by GeneCards, OMIM and TTD database. The intersection of drug and disease targets was obtained by online software Draw Venn Diagram, and the intersection tar-gets were imported into David 6.8 for GO and KEGG function enrichment analysis. Construction of protein-protein interaction network through STRING database, Cytoscape software was used to screen hub genes. Molecular docking analysis of hub genes was carried out with AutoDock Vina software. Results: A total of 13 active components were screened out from ASH and 103 drug and disease intersection targets were screened. Finally, 10 hub targets including CDKN1A, CDK2, JUN, E2F1, RB1, TNF, IL6, CCNA2, IL1B and CXCL8 were screened out. The hub targets were docked well with some active components. Conclusion: The active components of ASH are involved in regulating cell cycle, inflammatory response, cancer and other signaling pathways by acting on CDKN1A, CDK2, CXCL8 and other targets, which may play a role in the treatment of liver cancer.

References

[1]  Liu, M., Yan, Q., Sun, Y., Nam, Y., Hu, L., Loong, J.H.C., et al. (2020) A Hepatocyte Differentiation Model Reveals Two Subtypes of Liver Cancer with Different Oncofetal Properties and Therapeutic Targets. Proceedings of the National Academy of Sciences of the United States of America, 117, 6103-6113.
https://doi.org/10.1073/pnas.1912146117
[2]  Shibata, T. and Aburatani, H. (2014) Exploration of Liver Cancer Genomes. Nature Reviews. Gastroenterology & Hepatology, 11, 340-349.
https://doi.org/10.1038/nrgastro.2014.6
[3]  Ali, E.S., Rychkov, G.Y. and Barritt, G.J. (2019) Deranged Hepatocyte Intracellular Ca2+ Homeostasis and the Progression of Non-Alcoholic Fatty Liver Disease to Hepatocellular Carcinoma. Cell calcium, 82, Article ID: 102057.
https://doi.org/10.1016/j.ceca.2019.102057
[4]  Zhu, C.P., Wang, A.Q., Zhang, H.H., Wan, X.-S., Yang, X.-B., Zhao, H.-T., et al. (2015) Research Progress and Prospects of Markers for Liver Cancer Stem Cells. World Journal of Gastroenterology, 21, 12190-12196.
https://doi.org/10.3748/wjg.v21.i42.12190
[5]  Anwanwan, D., Singh, S.K., Singh, S., Saikam, V. and Singh, R. (2020) Challenges in Liver Cancer and Possible Treatment Approaches. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1873, Article ID: 188314.
https://doi.org/10.1016/j.bbcan.2019.188314
[6]  Yang, W.S., Zeng, X.F., Liu, Z.N., Zhao, Q.-H., Tan, Y.T., Gao, J., et al. (2020) Diet and Liver Cancer Risk: A Narrative Review of Epidemiological Evidence. The British Journal of Nutrition, 124, 330-340.
https://doi.org/10.1017/S0007114520001208
[7]  Ringelhan, M., McKeating, J.A. and Protzer, U. (2017) Viral Hepatitis and Liver Cancer. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 372, Article ID: 20160274.
https://doi.org/10.1098/rstb.2016.0274
[8]  Jeong, S., Zheng, B., Wang, H., Xia, Q. and Chen, L. (2018) Nervous System and Primary Liver Cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1869, 286-292.
https://doi.org/10.1016/j.bbcan.2018.04.002
[9]  Wang, H., Lu, Z. and Zhao, X. (2019) Tumorigenesis, Diagnosis, and Therapeutic Potential of Exosomes in Liver Cancer. Journal of Hematology & Oncology, 12, Article No. 133.
https://doi.org/10.1186/s13045-019-0806-6
[10]  Sung, K.C., Johnston, M.P., Lee, M.Y. and Byrne, C.D. (2020) Non-Invasive Liver Fibrosis Scores Are Strongly Associated with Liver Cancer Mortality in General Population without Liver Disease. Liver International, 40, 1303-1315.
https://doi.org/10.1111/liv.14416
[11]  Yin, Z., Huang, J., Ma, T., Li, D., Wu, Z., Hou, B., et al. (2017) Macrophages Activating Chemokine (C-X-C Motif) Ligand 8/miR-17 Cluster Modulate Hepatocellular Carcinoma Cell Growth and Metastasis. American Journal of Translational Research, 9, 2403-2411.
[12]  刘玉萍, 邱小玉, 刘烨, 马国. 茵陈的药理作用研究进展[J]. 中草药, 2019, 50(9): 2235-2241.
[13]  Kim, J., Jung, K.H., Yan, H.H., Cheon, M.J., Kang, S., Jin, X., et al. (2018) Artemisia Capillaris Leaves Inhibit Cell Proliferation and Induce Apoptosis in Hepatocellular Carcinoma. BMC Complementary and Alternative Medicine, 18, Article No. 147.
https://doi.org/10.1186/s12906-018-2217-6
[14]  Jung, K.H., Rumman, M., Yan, H., Cheon, M.J., Choi, J.G., Jin, X., et al. (2018) An Ethyl Acetate Fraction of Artemisia capillaris (ACE-63) Induced Apoptosis and Anti-Angiogenesis via Inhibition of PI3K/AKT Signaling in Hepatocellular Carcinoma. Phytotherapy Research, 32, 2034-2046.
https://doi.org/10.1002/ptr.6135
[15]  Yan, H., Jung, K.H., Kim, J., Rumman, M., Oh, M.S. and Hong, S. (2018) Artemisia capillaris Extract AC68 Induces Apoptosis of Hepatocellular Carcinoma by Blocking the PI3K/AKT Pathway. Biomedicine & Pharmacotherapy, 98, 134-141.
https://doi.org/10.1016/j.biopha.2017.12.043
[16]  Jang, E., Kim, B.J., Lee, K.T., Inn, K.-S. and Lee, J.-H. (2015) A Survey of Therapeutic Effects of Artemisia capillaris in Liver Diseases. Evidence-Based Complementary and Alternative Medicine, 2015, Article ID: 728137.
https://doi.org/10.1155/2015/728137
[17]  胡泽明, 陈彪, 钟佳宁, 陈斌. 原发性肝癌治疗方法的应用进展[J]. 山东医药, 2019, 59(9): 106-110.
[18]  Wang, X., Wang, N., Cheung, F., Lao, L., Li, C. and Feng, Y. (2015) Chinese Medicines for Prevention and Treatment of Human Hepatocellular Carcinoma: Current Progress on Pharmacological Actions and Mechanisms. Journal of Integrative Medicine, 13, 142-164.
https://doi.org/10.1016/S2095-4964(15)60171-6
[19]  Samec, M., Liskova, A., Koklesova, L., Samuel, S.M., Zhai, K., Buhrmann, C., et al. (2020) Flavonoids against the Warburg Phenotype-Concepts of Predictive, Preventive and Personalised Medicine to Cut the Gordian Knot of Cancer Cell Metabolism. The EPMA Journal, 11, 377-398.
https://doi.org/10.1007/s13167-020-00217-y
[20]  Liao, C.Y., Lee, C.C., Tsai, C.C., Hsueh, C.-W., Wang, C.-C., Chen, I-H., et al. (2015) Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma. BioMed Research International, 2015, Article ID: 840542.
https://doi.org/10.1155/2015/840542
[21]  Silva, C.F.M., Batista, V.F., Pinto, D. and Silva, A.M.S. (2018) Challenges with Chromone as a Privileged Scaffold in drug Discovery. Expert Opinion on Drug Discovery, 13, 795-798.
https://doi.org/10.1080/17460441.2018.1494720
[22]  刘双利, 姜程曦, 赵岩, 许永华, 王壮, 张连学. 防风化学成分及其药理作用研究进展[J]. 中草药, 2017, 48(10): 2146-2152.
[23]  Shahzad, N., Khan, W., Md, S., Ali, A., Singh Saluja, S., Sharma, S., et al. (2017) Phytosterols as a Natural Anticancer Agent: Current Status and Future Perspective. Biomedicine & Pharmacotherapy, 88, 786-794.
https://doi.org/10.1016/j.biopha.2017.01.068
[24]  Plat, J., Hendrikx, T., Bieghs, V., Jeurissen, M.L.J., Walenbergh, S.M.A., van Gorp, P.J., et al. (2014) Protective Role of Plant Sterol and Stanol Esters in Liver Inflammation: Insights from Mice and Humans. PLoS ONE, 9, e110758.
https://doi.org/10.1371/journal.pone.0110758
[25]  Sun, X., Hu, Y., Wu, J., Shi, L., Zhu, L., Xi, P.-W., et al. (2018) RBMS2 Inhibits the Proliferation by Stabilizing P21 mRNA in Breast Cancer. Journal of Experimental & Clinical Cancer Research, 37, Article No. 298.
https://doi.org/10.1186/s13046-018-0968-z
[26]  Ehedego, H., Boekschoten, M.V., Hu, W., Doler, C., Haybaeck, J., Gaβler, N., et al. (2015) p21 Ablation in Liver Enhances DNA Damage, Cholestasis, and Carcinogenesis. Cancer Research, 75, 1144-1155.
https://doi.org/10.1158/0008-5472.CAN-14-1356
[27]  Diao, P.C., Lin, W.Y., Jian, X.E., Li, Y.-H., You, W.-W., Jian, X.-E., et al. (2019) Discovery of Novel Pyrimidine-Based Benzothiazole Derivatives as Potent Cyclin-Dependent Kinase 2 Inhibitors with Anticancer Activity. European Journal of Medicinal Chemistry, 179, 196-207.
https://doi.org/10.1016/j.ejmech.2019.06.055
[28]  Mahajan, P., Chashoo, G., Gupta, M., Kumar, A., Pal Singh, P. and Nargotra, A. (2017) Fusion of Structure and Ligand Based Methods for Identification of Novel CDK2 Inhibitors. Journal of Chemical Information and Modeling, 57, 1957-1969.
https://doi.org/10.1021/acs.jcim.7b00293
[29]  Lian, J., Zhang, X., Lu, Y., Hao, S., Zhang, Z. and Yang, Y. (2019) Expression and Significance of LncRNA-MINCR and CDK2 mRNA in Primary Hepatocellular Carcinoma. Combinatorial Chemistry & High Throughput Screening, 22, 201-206.
https://doi.org/10.2174/1386207322666190404151020
[30]  朱继业, 秦致中, 王东, 栗光明, 高杰, 冷希圣, 杜如昱. 人肝癌组织中核内转录基因Fos B和Jun D的表达及其意义[J]. 中华普通外科杂志, 2001, 16(1): 14-16.
[31]  He, Y., Huang, S., Cheng, T., Wang, Y., Zhou, S.-J., Zhang, Y.-M., et al. (2020) High Glucose May Promote the Proliferation and Metastasis of Hepatocellular Carcinoma via E2F1/RRBP1 Pathway. Life Sciences, 252, Article ID: 117656.
https://doi.org/10.1016/j.lfs.2020.117656
[32]  Kent, L.N., Bae, S., Tsai, S.Y., Tang, X., Srivastava, A., Koivisto, C., et al. (2017) Dosage-Dependent Copy Number Gains in E2f1 and E2f3 Drive Hepatocellular Carcinoma. The Journal of Clinical Investigation, 127, 830-842.
https://doi.org/10.1172/JCI87583
[33]  Liu, C., Wang, C., Wang, J. and Huang, H. (2016) miR-1297 Promotes Cell Proliferation by Inhibiting RB1 in Liver Cancer. Oncology Letters, 12, 5177-5182.
https://doi.org/10.3892/ol.2016.5326
[34]  Anwar, S.L., Krech, T., Hasemeier, B., Schipper, E., Schweitzer, N., Vogel, A., et al. (2014) Deregulation of RB1 Expression by Loss of Imprinting in Human Hepatocellular Carcinoma. The Journal of Pathology, 233, 392-401.
https://doi.org/10.1002/path.4376
[35]  Jing, Y., Sun, K., Liu, W., Sheng, D., Zhao, S., Gao, L., et al. (2018) Tumor Necrosis Factor-α Promotes Hepatocellular Carcinogenesis through the Activation of Hepatic Progenitor Cells. Cancer Letters, 434, 22-32.
https://doi.org/10.1016/j.canlet.2018.07.001
[36]  Chen, S., Tang, Y., Yang, C., Li, K., Huang, X. and Cao, J. (2020) Silencing CDC25A Inhibits the Proliferation of Liver Cancer Cells by Downregulating IL-6 in Vitro and in Vivo. International Journal of Molecular Medicine, 45, 743-752.
https://doi.org/10.3892/ijmm.2020.4461
[37]  Bayard, Q., Meunier, L., Peneau, C., Renault, V., Shinde, J., Nault, J.-C., et al. (2018) Cyclin A2/E1 Activation Defines a Hepatocellular Carcinoma Subclass with a Rearrangement Signature of Replication Stress. Nature Communications, 9, Article No. 5235.
https://doi.org/10.1038/s41467-018-07552-9
[38]  Gopinathan, L., Tan, S.L., Padmakumar, V.C., Coppola, V., Tessarollo, L. and Kaldis, P. (2014) Loss of Cdk2 and Cyclin A2 Impairs Cell Proliferation and Tumorigenesis. Cancer Research, 74, 3870-3879.
https://doi.org/10.1158/0008-5472.CAN-13-3440
[39]  Qian, H., Zhang, D. and Bao, C. (2018) Two Variants of Interleukin-1B Gene Are Associated with the Decreased Risk, Clinical Features, and Better Overall Survival of Colorectal Cancer: A Two-Center Case-Control Study. Aging, 10, 4084-4092.
https://doi.org/10.18632/aging.101695
[40]  He, B., Zhang, Y., Pan, Y., Xu, Y., Gu, L., Chen, L., et al. (2011) Interleukin 1 Beta (IL1B) Promoter Polymorphism and Cancer Risk: Evidence from 47 Published Studies. Mutagenesis, 26, 637-642.
https://doi.org/10.1093/mutage/ger025
[41]  Yang, S., Wang, H., Qin, C., Sun, H. and Han, Y. (2020) Up-Regulation of CXCL8 Expression Is Associated with a Poor Prognosis and Enhances Tumor Cell Malignant Behaviors in Liver Cancer. Bioscience Reports, 40, Article ID: BSR20201169.
https://doi.org/10.1042/BSR20201169

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133