山东第二医科大学中医学院;
乳腺癌(BC)是女性最常见的恶性肿瘤,中药治疗乳腺癌具有“多成分”和“多靶点”的特点,但中药成分、基因与疾病之间的关联机制难以揭示。网络药理学分子对接技术通过构建“药物-成分-靶点-通路-疾病”网络,从分子层面解释中药活性成分、靶点、通路与疾病间的关系,从而阐明中药治疗乳腺癌的作用机制。本文综述了网络药理学分子对接技术的研究步骤、基于分子对接技术的中药治疗乳腺癌相关信号通路研究进展以及治疗乳腺癌的中药成分和靶点分析,深入剖析了其中关键的分子作用靶点与潜在的调控机制,为中药治疗BC的作用机制研究提供参考。
176 | 0 | 31 |
下载次数 | 被引频次 | 阅读次数 |
[1] Sung H,Ferlay J,Siegel RL,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] Akram M,Iqbal M,Daniyal M,et al.Awareness and current knowledge of breast cancer[J].Biol Res,2017,50(1):33.
[3] Wu K,Zhu Z,He Y,et al.Efficacy and safety of Xiao Ai Ping injection combined with chemotherapy in advanced gastric cancer:a systematic review and meta-analysis[J].Evid Based Complement Alternat Med,2019,2019:3 821 053.
[4] Chen S,Wu S,Li W,et al.Investigation of the therapeutic effectiveness of active components in Sini decoction by a comprehensive GC/LC-MS based metabolomics and network pharmacology approaches[J].Mol Biosyst,2014,10(12):3310-3321.
[5] Zhang B,Wang X,Li S.An integrative platform of TCM network pharmacology and its application on a herbal formula,Qing-Luo-Yin[J].Evid Based Complement Alternat Med,2013:456 747.
[6] Nicholson KM,Anderson NG.The protein kinase B/Akt signalling pathway in human malignancy[J].Cell Signal,2002,14(5):381-395.
[7] Zhu K,Wu Y,He P,et al.PI3K/AKT/mTOR-Targeted therapy for breast cancer[J].Cells,2022,11(16):2508.
[8] Chu M,Meng T,Zhou Y,et al.Molecular mechanism of Ruxian Shuhou prescription in the treatment of triple-negative breast cancer based on network pharmacology[J].Medicine(Baltimore),2023,102(35):e34763.
[9] Schon K,Tischkowitz M.Clinical implications of germline mutations in breast cancer:TP53[J].Breast Cancer Res Treat,2018,167(2):417-423.
[10] Choi SK,Kim HS,Jin T,et al.Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A[J].BMC cancer,2016,16:570.
[11] Hu Y,He J,Xu Y.Network pharmacology study on the underlying mechanism of Danggui-Kushen herb pair in adjuvant chemotherapeutics against breast cancer[J].Comb Chem High Throughput Screen,2024.
[12] Won YS,Seo KI.Lupiwighteone induces caspase-dependent and -independent apoptosis on human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway[J].Food Chem Toxicol,2020,135:110 863.
[13] Mamot C,Wicki A,Hasler-Strub U,et al.A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer[J].Sci Rep,2023,13(1):3705.
[14] Luo L,Chen Y,Ma Q,et al.Exploring the mechanism of an active ingredient of ginger,dihydrocapsaicin,on triple negative breast cancer based on network pharmacology and in vitro experiments[J].Oncol Lett,2023,25(5):195.
[15] Wang S,Hao HF,Jiao YN,et al.Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism [J].Front Pharmacol,2022,13:942 996.
[16] Bai H,Wang R,Li Y,et al.Network pharmacology analysis,molecular docking,and in vitro verification reveal the action mechanism of prunella vulgaris Lin treating breast cance [J].Evid Based Complement Alternat Med,2022,2022:5 481 563.
[17] Gilmore TD.Introduction to NF-kappaB:players,pathways,perspectives[J].Oncogene,2006,25(51):6680-6684.
[18] Guo Y,Zhang Y,Yang X,et al.Effects of methylglyoxal and glyoxalase I inhibition on breast cancer cells proliferation,invasion,and apoptosis through modulation of MAPKs,MMP9,and Bcl-2[J].Cancer Biol Ther,2016,17(2):169-180.
[19] Liu J,Zhang C,Liu S,et al.Tanshinone IIA promotes apoptosis by downregulating BCL2 and upregulating TP53 in triple-negative breast cancer[J].Naunyn Schmiedebergs Arch Pharmacol,2023,396(2):365-374.
[20] Jackson-Fisher AJ,Bellinger G,Breindel JL,et al.ErbB3 is required for ductal morphogenesis in the mouse mammary gland[J].Breast Cancer Res,2008,10(6):R96.
[21] Balko JM,Miller TW,Morrison MM,et al.The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium[J].Proc Natl Acad Sci U S A,2012,109(1):221-226.
[22] Lai AZ,Abella JV,Park M.Crosstalk in Met receptor oncogenesis[J].Trends Cell Biol,2009,19(10):542-551.
[23] Alles MC,Gardiner-Garden M,Nott DJ,et al.Meta-analysis and gene set enrichment relative to er status reveal elevated activity of MYC and E2F in the "basal" breast cancer subgroup[J].PloS One,2009,4(3):e4710.
[24] Magri L,Swiss VA,Jablonska B,et al.E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation[J].J Neurosci,2014,34(4):1481-1493.
[25] Ma Y,Peng Z,Pan R,et al.The bioinformatics analysis of quercetin in octagonal lotus for the screening of breast cancer MYC,CXCL10,CXCL11,and E2F1[J].Int J Immunopathol Pharmacol,2021,35:20587384211040903.
[26] Tsai WB,Aiba I,Long Y,et al.Activation of Ras/PI3K/ERK pathway induces c-Myc stabilization to upregulate argininosuccinate synthetase,leading to arginine deiminase resistance in melanoma cells[J].Cancer Res,2012,72(10):2622-2633.
[27] Ye X,Zhou J,Tong D,et al.E2f1 affects the therapeutic response to neoadjuvant therapy in breast cancer[J].Dis Markers,2022,2022:8 168 517.
[28] Sun EG,Vijayan V,Park MR,et al.Suppression of triple-negative breast cancer aggressiveness by LGALS3BP via inhibition of the TNF-alpha-TAK1-MMP9 axis[J].Cell Death Discov,2023,9(1):122.
[29] Fan T,Huang Y,Liu Z,et al.Unveiling the mechanism of the ChaiShao Shugan formula against triple-negative breast cancer[J].Drug Des Devel Ther,2024,18:1115-1131.
[30] Weidner N,Semple JP,Welch WR,et al.Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma[J].N Engl J Med,1991,324(1):1-8.
[31] Lee SO,Jeong YJ,Yu MH,et al.Wogonin suppresses TNF-alpha-induced MMP-9 expression by blocking the NF-kappaB activation via MAPK signaling pathways in human aortic smooth muscle cells[J].Biochem Biophys Res Commun,2006,351(1):118-125.
[32] Liu S,Hu X,Fan X,et al.A bioinformatics research on novel mechanism of compound Kushen injection for treating breast cancer by network pharmacology and molecular docking verification[J].Evid Based Complement Alternat Med,2020,2020:2 758 640.
[33] Kim S,Choi JH,Kim JB,et al.Berberine suppresses TNF-alpha-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells[J].Molecules,2008,13(12):2975-2985.
[34] 吴沁航,朱丽文,陈子慧,等.基于网络药理学及实验验证探析雷公藤治疗三阴性乳腺癌的分子机制[J].中国实验方剂学杂志,2022,28(6):131-141.
[35] Dailey GP,Rabiola CA,Lei G,et al.Vaccines targeting ESR1 activating mutations elicit anti-tumor immune responses and suppress estrogen signaling in therapy resistant ER+ breast cancer[J].Hum Vaccin Immunother,2024,20(1):2 309 693.
[36] Clemons M,Goss P.Estrogen and the risk of breast cancer[J].New Engl J Med,2001,344(4):276-285.
[37] Theocharis AD,Skandalis SS,Neill T,et al.Insights into the key roles of proteoglycans in breast cancer biology and translational medicine[J].Biochim Biophys Acta,2015,1855(2):276-300.
[38] Xie YI,Tang C,Qin JP,et al.Molecular docking technology and network pharmacology based on Rhapontici Radix-Cremastrae Pseudobulbus drug pair in treating breast cancer[J].Eur Rev Med Pharmacol Sci,2023,27(21):10 204-10 212.
[39] Toy W,Weir H,Razavi P,et al.Activating ESR1 mutations differentially affect the efficacy of ER antagonists[J].Cancer Discov,2017,7(3):277-287.
[40] Liu H,Zhang Z,Huang Y,et al.Plasma HSP90AA1 predicts the risk of breast cancer onset and distant metastasis[J].Front Cell Dev Biol,2021,9:639 596.
[41] Grinshpun A,Sandusky Zm,Jeselsohn R.The clinical utility of ESR1 mutations in hormone receptor-positive,HER2-negative advanced breast cancer [J].Hematol Oncol Clin North Am,2023,37(1):169-181.
[42] Shang Y,Hu X,DiRenzo J,et al.Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription[J].Cell,2000,103(6):843-852.
[43] Shiu Rp,Watson Ph,Dubik D.C-myc oncogene expression in estrogen-dependent and -independent breast cancer[J].Clin Chem,1993,39(2):353-355.
[44] Rounbehler Rj,Fallahi M,Yang C,et al.Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state[J].Cell,2012,150(3):563-574.
[45] Manore SG,Doheny DI,Wong GL,et al.IL-6/JAK/STAT3 signaling in breast cancer metastasis:biology and treatment[J].Front Oncol,2022,12:866 014.
[46] Huang H.Matrix Metalloproteinase-9(MMP-9) as a cancer biomarker and Mmp-9 biosensors:recent advances[J].Sensors(Basel),2018,18(10):3249.
[47] Huang B,Wen G,Li R,et al.Integrated network pharmacology,bioinformatics,and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer[J].Medicine(Baltimore),2023,102(36):e35070.
[48] Li F,Shi Y,Yang X,et al.Anhydroicaritin inhibits EMT in breast cancer by enhancing GPX1 expression:a research based on sequencing technologies and bioinformatics analysis[J].Front Cell Dev Biol,2022,9:764 481.
[49] Wu C,Sun C,Han X,et al.Sanyin formula enhances the therapeutic efficacy of paclitaxel in triple-negative breast cancer metastases through the JAK/STAT3 Pathway in Mice[J].Pharmaceuticals(Basel),2022,16(1):9.
[50] Yuan J,Lin M,Yang S,et al.The therapeutic effect and targets of herba Sarcandrae on breast cancer and the construction of a prognostic signature consisting of inflammation-related genes[J].Heliyon,2024,10(10):e31137.
[51] Wu Z,Wu J,Zhao Q,et al.Emerging roles of aerobic glycolysis in breast cancer[J].Clin Transl Oncol,2020,22(5):631-646.
[52] Moreira J,Almeida J,Saraiva L,et al.Chalcones as promising antitumor agents by targeting the p53 pathway:an overview and new insights in drug-likeness[J].Molecules,2021,26(12):3737.
[53] Ismail NZ,Khairuddean M,Abubakar S,et al.Network pharmacology,molecular docking and molecular dynamics simulation of chalcone scaffold-based compounds targeting breast cancer receptors[J].J Biomol Struct Dyn,2023,12:1-16.
[54] Chiang Y,Morales M,Zhou FC,et al.Fetal intra-nigral ventral mesencephalon and kidney tissue bridge transplantation restores the nigrostriatal dopamine pathway in hemi-parkinsonian rats[J].Brain Res,2001,889(1-2):200-207.
[55] Xu Y,Zhang YX,Chen HY,et al.Integrating network pharmacology and in vivo experimental validation to reveal the mechanism of FuZheng YiLiu Formula on estrogen receptor positive breast cancer[J].Comb Chem High Throughput Screen,2023.
[56] Tadesse S,Anshabo At,Portman N,et al.Targeting CDK2 in cancer:challenges and opportunities for therapy[J].Drug Discov Today,2020,25(2):406-413.
[57] Lashen A,Alqahtani S,Shoqafi A,et al.Clinicopathological significance of cyclin-dependent Kinase 2(CDK2) in ductal carcinoma in situ and early-stage invasive breast cancers[J].Int J Mol Sci,2024,25(9):5053.
[58] Wang J,Yang T,Xu G,et al.Cyclin-dependent Kinase 2 promotes tumor proliferation and induces radio resistance in glioblastoma[J].Transl Oncol,2016,9(6):548-556.
[59] Carroll JS,Prall OW,Musgrove EA,et al.A pure estrogen antagonist inhibits cyclin E-Cdk2 activity in MCF-7 breast cancer cells and induces accumulation of p130-E2F4 complexes characteristic of quiescence[J].J Biol Chem,2000,275(49):38 221-38 229.
[60] Li ZH,Yang GH,Wang F.Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety:A network pharmacology and molecular docking study[J].World J Clin Cases,2022,10(33):12 104-12 115.
[61] Linzen U,Lilischkis R,Pandithage R,et al.ING5 is phosphorylated by CDK2 and controls cell proliferation independently of p53[J].PloS one,2015,10(4):e0123736.
[62] Liu C,Li H,Wang K,et al.Identifying the antiproliferative effect of astragalus polysaccharides on breast cancer:coupling network pharmacology with targetable screening from the cancer genome atlas[J].Front Oncol,2019,9:368.
[63] Wu Y,Zhou T,Qian D,et al.Z-Guggulsterone induces cell cycle arrest and apoptosis by targeting the p53/CCNB1/PLK1 pathway in triple-negative breast cancer[J].ACS omega,2023,8(2):2780-2792.
[64] Abdelgalil AA,Monir R,Elmetwally M,et al.The relation of VEGFA,VEGFR2,VEGI,and HIF1A genetic variants and their serum protein levels with breast cancer in egyptian patients[J].Biochem Genet,2024,62(1):547-573.
[65] Bahamin N,Rafieian-Kopaei M,Ahmadian S,et al.Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1alpha/VEGF mediated tumor angiogenesis in vivo[J].Heliyon,2023,9(5):e16292.
[66] Zhao J,Zhang H,Liu Y,et al.HIF-1alpha knockdown suppresses breast cancer metastasis via epithelial mesenchymal transition Abrogation [J].heliyon,2024,10(19):e37900.
[67] Rankin Eb,Wu C,Khatri R,et al.The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO[J].Cell,2012,149(1):63-74.
[68] Ferrara N,Davis-Smyth T.The biology of vascular endothelial growth factor[J].Endocr Rev,1997,18(1):4-25.
[69] Kakeya H,Osada H.Development of novel angiogenesis inhibitors targeting VEGF(vascular endothelial growth factor) for cancer chemotherapy[J].Nihon Rinsho,2004,62(7):1264-1270.
[70] Shi Y,Wu Y,Li F,et al.Identifying the anti-metastasis effect of Anhydroicaritin on breast cancer:Coupling network pharmacology with experimental validation[J].Ethnopharmacol,2022,293:115 326.
[71] Chen L,Yang A,Li Y,et al.Molecular mechanism of oroxyli semen against triple-negative breast cancer verified by bioinformatics and in vitro experiments[J].Medicine(Baltimore),2023,102(37):e34835.
[72] Wadowska K,B?asiak P,Rzechonek A,et al.Analysis of MMP-2-735C/T(rs2285053) and MMP-9-1562C/T(rs3918242) polymorphisms in the risk assessment of developing lung cancer[J].Int J Mol Sci,2023,24(13):10 576.
[73] Amelio I,Mancini M,Petrova V,et al.P53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression[J].Proc Natl Acad Sci USA,2018,115(46):E10869-E10878.
[74] Jiao Y,Shi C,Sun Y.Unraveling the role of scutellaria baicalensis for the treatment of breast cancer using network pharmacology,molecular docking,and molecular dynamics simulation[J].Int J Mol Sci,2023,24(4):3594.
[75] Huang S,Chen Y,Pan L,et al.Exploration of the potential mechanism of Tao Hong Si Wu decoction for the treatment of breast cancer based on network pharmacology and in vitro experimental verification[J].Front Oncol,2021,11:731 522.
[76] Smit L,Berns K,Spence K,et al.An integrated genomic approach identifies that the PI3K/AKT/FOXO pathway is involved in breast cancer tumor initiation[J].Oncotarget,2016,7(3):2596-2610.
[77] Xu J,Lamouille S,Derynck R.TGF-beta-induced epithelial to mesenchymal transition[J].Cell Res,2009,19(2):156-172.
[78] Luo D,Zeng X,Zhang S,et al.Pirfenidone suppressed triple-negative breast cancer metastasis by inhibiting the activity of the TGF-beta/SMAD pathway[J].J Cell Mol Med,2023,27(3):456-469.
[79] Zhang Y,Shi K,Liu H,et al.MiR-4458 inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells by suppressing the TGF-beta signaling pathway via targeting TGFBR1[J].Acta Biochim Biophys Sin(Shanghai),2020,52(5):554-562.
[80] Li H,Shi W,Shen T,et al.Network pharmacology-based strategy for predicting therapy targets of Ecliptae Herba on breast cancer[J].Medicine(Baltimore),2023,102(41):e35384.
[81] Gramatzki D,Pantazis G,Schittenhelm J,et al.Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells [J].Oncogene,2009,28(28):2593-2605.
[82] Kerzee JK,Ramos KS.Constitutive and inducible expression of Cyp1a1 and Cyp1b1 in vascular smooth muscle cells:role of the Ahr bHLH/PAS transcription factor[J].Circ Res,2001,89(7):573-582.
[83] Zhang N,Wang J,Sheng A,et al.Emodin inhibits the proliferation of mcf-7 human breast cancer cells through activation of Aryl hydrocarbon receptor(AhR)[J].Front Pharmacol,2020,11:622 046.
[84] Barrallo-Gimeno A,Nieto Ma.The Snail genes as inducers of cell movement and survival:implications in development and cancer[J].Development,2005,132(14):3151-3161.
[85] Yang HW,Menon LG,Black PM,et al.SNAI2/Slug promotes growth and invasion in human gliomas[J].BMC Cancer,2010,10:301.
[86] Zibara K,Zeidan A,Bjeije H,et al.ROS mediates interferon gamma induced phosphorylation of Src,through the Raf/ERK pathway,in MCF-7 human breast cancer cell line[J].J Cell Commun Signal,2017,11(1):57-67.
[87] Chen H,Zhu G,Li Y,et al.Extracellular signal-regulated kinase signaling pathway regulates breast cancer cell migration by maintaining slug expression[J].Cancer Res,2009,69(24):9228-9235.
[88] Xia YT,Zhang YQ,Chen L,et al.Suppression of migration and invasion by taraxerol in the triple-negative breast cancer cell line MDA-MB-231 via the ERK/Slug axis[J].PloS One,2023,18(9):e0291693.
[89] Li X,Zhou N,Wang J,et al.Quercetin suppresses breast cancer stem cells(CD44(+)/CD24(-)) by inhibiting the PI3K/Akt/mTOR-signaling pathway[J].Life Sci,2018,196:56-62.
[90] Cook MT,Liang Y,Besch-Williford C,et al.Luteolin inhibits lung metastasis,cell migration,and viability of triple-negative breast cancer cells[J].Breast Cancer(Dove Med Press),2016,9:9-19.
[91] Wu HT,Lin J,Liu YE,et al.Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway[J].Phytomedicine,2021,81:153 437.
[92] Jeon YW,Ahn YE,Chung WS,et al.Synergistic effect between celecoxib and luteolin is dependent on estrogen receptor in human breast cancer cells[J].Tumour Biol,2015,36(8):6349-6359.
[93] Hih YL,Liu HC,Chen CS,et al.Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by down-regulating nicotinic acetylcholine receptors[J].J Agric Food Chem,2010,58(1):235-241.
[94] Khan Z,Nath N,Rauf A,et al.Multifunctional roles and pharmacological potential of beta-sitosterol:Emerging evidence toward clinical applications[J].Chem Biol Interact,2022,365:110 117.
[95] Wang KN,Hu Y,Han LL,et al.Salvia chinensis benth inhibits triple-negative breast cancer progression by inducing the DNA damage pathway[J].Front Oncol,2022,12:882 784.
[96] Bakrim S,Benkhaira N,Bourais I,et al.Health benefits and pharmacological properties of stigmasterol[J].Antioxidants(Basel),2022,11(10):1912.
[97] Hu S,Huang L,Meng L,et al.Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogen activated protein kinase kinase signaling pathways[J].Mol Med Rep,2015,12(5):6745-6751.
[98] Zhang HW,Lv C,Zhang LJ,et al.Application of omics- and multi-omics-based techniques for natural product target discovery[J].Biomed Pharmacother,2021,141:111 833.
基本信息:
DOI:10.16846/j.issn.1004-3101.2025.01.015
中图分类号:R285
引用信息:
[1]白宛鑫,张文泽,杜子涵等.基于网络药理学及分子对接技术的中药治疗乳腺癌作用机制研究进展[J].山东第二医科大学学报,2025,47(01):69-76.DOI:10.16846/j.issn.1004-3101.2025.01.015.
基金信息:
山东省高等学校青年创新团队发展计划(项目编号:2023KJ256)