Evaluation of the Mechanism of Yishan Formula in Treating Breast Cancer Based on Network Pharmacology and Experimental Verification
- 作者: Lin X.1, Chi W.2, Geng X.2, Jiang Q.2, Ma B.2, Dai B.2, Sui Y.3, Jiang J.4
-
隶属关系:
- Oncology, Heilongjiang University of Chinese Medicine
- , Heilongjiang University of Chinese Medicine
- , Shenzhen Hospital of Southern Medical University
- , Heilongjiang University of Chinese Medicine,
- 期: 卷 27, 编号 17 (2024)
- 页面: 2583-2597
- 栏目: Chemistry
- URL: https://rjeid.com/1386-2073/article/view/645273
- DOI: https://doi.org/10.2174/0113862073266004231105164321
- ID: 645273
如何引用文章
全文:
详细
Background:Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown.
Objective:In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments.
Methods:Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes.
Results:Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (AKT1, TP53, TNF, IL6, EGFR, SRC, VEGFA, STAT3, MAPK3, and JUN) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes.
Conclusion:This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.
作者简介
Xiaoyue Lin
Oncology, Heilongjiang University of Chinese Medicine
Email: info@benthamscience.net
Wencheng Chi
, Heilongjiang University of Chinese Medicine
Email: info@benthamscience.net
Xue Geng
, Heilongjiang University of Chinese Medicine
Email: info@benthamscience.net
Qinghui Jiang
, Heilongjiang University of Chinese Medicine
Email: info@benthamscience.net
Baozhu Ma
, Heilongjiang University of Chinese Medicine
Email: info@benthamscience.net
Bowen Dai
, Heilongjiang University of Chinese Medicine
Email: info@benthamscience.net
Yutong Sui
, Shenzhen Hospital of Southern Medical University
编辑信件的主要联系方式.
Email: info@benthamscience.net
Jiakang Jiang
, Heilongjiang University of Chinese Medicine,
编辑信件的主要联系方式.
Email: info@benthamscience.net
参考
- Yang, W.J.; Zhang, G.L.; Cao, K.X.; Liu, X.N.; Wang, X.M.; Yu, M.W.; Li, J.P.; Yang, G.W. Heparanase from triple negative breast cancer and platelets acts as an enhancer of metastasis. Int. J. Oncol., 2020, 57(4), 890-904. doi: 10.3892/ijo.2020.5115 PMID: 32945393
- Trapani, D.; Ginsburg, O.; Fadelu, T.; Lin, N.U.; Hassett, M.; Ilbawi, A.M.; Anderson, B.O.; Curigliano, G. Global challenges and policy solutions in breast cancer control. Cancer Treat. Rev., 2022, 104, 102339. doi: 10.1016/j.ctrv.2022.102339 PMID: 35074727
- Jordan, R.M.; Oxenberg, J. Breast Cancer Conservation Therapy; StatPearls: Treasure Island, FL, 2022.
- Luo, H.; Vong, C.T.; Chen, H.; Gao, Y.; Lyu, P.; Qiu, L.; Zhao, M.; Liu, Q.; Cheng, Z.; Zou, J.; Yao, P.; Gao, C.; Wei, J.; Ung, C.O.L.; Wang, S.; Zhong, Z.; Wang, Y. Naturally occurring anti-cancer compounds: Shining from Chinese herbal medicine. Chin. Med., 2019, 14(1), 48. doi: 10.1186/s13020-019-0270-9 PMID: 31719837
- Mu, C.; Sheng, Y.; Wang, Q.; Amin, A.; Li, X.; Xie, Y. Potential compound from herbal food of rhizoma polygonati for treatment of COVID-19 analyzed by network pharmacology: Viral and cancer signaling mechanisms. J. Funct. Foods, 2021, 77, 104149. doi: 10.1016/j.jff.2020.104149 PMID: 32837538
- Chen, Z.; Lin, T.; Liao, X.; Li, Z.; Lin, R.; Qi, X.; Chen, G.; Sun, L.; Lin, L. Network pharmacology based research into the effect and mechanism of yinchenhao decoction against cholangiocarcinoma. Chin. Med., 2021, 16(1), 13. doi: 10.1186/s13020-021-00423-4 PMID: 33478536
- Kim, S.; Chen, J.; Cheng, T.; Gindulyte, A.; He, J.; He, S.; Li, Q.; Shoemaker, B.A.; Thiessen, P.A.; Yu, B.; Zaslavsky, L.; Zhang, J.; Bolton, E.E. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res., 2021, 49(D1), D1388-D1395. doi: 10.1093/nar/gkaa971 PMID: 33151290
- Li, W.H.; Han, J.R.; Ren, P.P.; Xie, Y.; Jiang, D.Y. Exploration of the mechanism of zisheng shenqi decoction against gout arthritis using network pharmacology. Comput. Biol. Chem., 2021, 90, 107358. doi: 10.1016/j.compbiolchem.2020.107358 PMID: 33243703
- Ma, T.C.; Ma, Y.K.; Zhang, J.L.; Liu, L.; Sun, J.; Guo, L.N.; Liu, Q.; Sun, Y. Integrated strategy of UHPLC-Q-TOF-MS and Molecular Networking for Identification of Diterpenoids from Euphorbia fischeriana Steud. and prediction of the anti-breast-cancer mechanism by the network pharmacological method. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-19. doi: 10.1155/2021/3829434 PMID: 34804177
- Liu, T.; Chen, W.; Chen, X.; Liang, Q.; Tao, W.; Jin, Z.; Xiao, Y.; Chen, L. Network pharmacology identifies the mechanisms of action of taohongsiwu decoction against essential hypertension. Med. Sci. Monit., 2020, 26, e920682. doi: 10.12659/MSM.920682 PMID: 32187175
- Wang, Y.; Zhang, S.; Li, F.; Zhou, Y.; Zhang, Y.; Wang, Z.; Zhang, R.; Zhu, J.; Ren, Y.; Tan, Y.; Qin, C.; Li, Y.; Li, X.; Chen, Y.; Zhu, F. Therapeutic target database 2020: Enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res., 2020, 48(D1), D1031-D1041. PMID: 31691823
- Mohan, S.; Mok, S.; Judge, T. Identification of novel therapeutic molecular targets in inflammatory bowel disease by using genetic databases. Clin. Exp. Gastroenterol., 2020, 13, 467-473. doi: 10.2147/CEG.S264812 PMID: 33116744
- Lv, X.; Xu, Z.; Xu, G.; Li, H.; Wang, C.; Chen, J.; Sun, J. Investigation of the active components and mechanisms of Schisandra chinensis in the treatment of asthma based on a network pharmacology approach and experimental validation. Food Funct., 2020, 11(4), 3032-3042. doi: 10.1039/D0FO00087F PMID: 32186565
- Cui, Q.K.; Li, H.; Li, Z.; Li, J.; Song, L. Study on the mechanism of the Modified Ginseng-Schisandra Decoction (MGSD) in the treatment of recurrent respiratory tract infection (RRTI) based on network pharmacology. Transl. Pediatr., 2021, 10(6), 1701-1711. doi: 10.21037/tp-21-240 PMID: 34295785
- Chen, Q.; Hu, J.; Deng, J.; Fu, B.; Guo, J. Bioinformatics analysis identified key molecular changes in bladder cancer development and recurrence. BioMed Res. Int., 2019, 2019, 1-14. doi: 10.1155/2019/3917982 PMID: 31828101
- Horvath, D.; Marcou, G.; Varnek, A. Generative topographic mapping of the docking conformational space. Molecules, 2019, 24(12), 2269. doi: 10.3390/molecules24122269 PMID: 31216756
- Eberhardt, J.; Santos-Martins, D.; Tillack, A.F.; Forli, S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model., 2021, 61(8), 3891-3898. doi: 10.1021/acs.jcim.1c00203 PMID: 34278794
- Mooers, B.H.M.; Brown, M.E. Templates for writing PYMOL scripts. Protein Sci., 2021, 30(1), 262-269. doi: 10.1002/pro.3997 PMID: 33179363
- Imran, M.; Salehi, B.; Sharifi-Rad, J.; Aslam Gondal, T.; Saeed, F.; Imran, A.; Shahbaz, M.; Tsouh Fokou, P.V.; Umair Arshad, M.; Khan, H.; Guerreiro, S.G.; Martins, N.; Estevinho, L.M. Kaempferol: A key emphasis to its anticancer potential. Molecules, 2019, 24(12), 2277. doi: 10.3390/molecules24122277 PMID: 31248102
- Wang, X.; Yang, Y.; An, Y.; Fang, G. The mechanism of anticancer action and potential clinical use of kaempferol in the treatment of breast cancer. Biomed. Pharmacother., 2019, 117, 109086. doi: 10.1016/j.biopha.2019.109086 PMID: 31200254
- Hu, G.; Liu, H.; Wang, M.; Peng, W. IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Kaempferol-induced apoptosis in breast cancer cells by extracellular signal-regulated kinases 1/2 (ERK1/2) signaling activation. Med. Sci. Monit., 2019, 25, 7666-7674. doi: 10.12659/MSM.915642 PMID: 31605603
- Ezzati, M.; Yousefi, B.; Velaei, K.; Safa, A. A review on anti-cancer properties of Quercetin in breast cancer. Life Sci., 2020, 248, 117463. doi: 10.1016/j.lfs.2020.117463 PMID: 32097663
- Qiu, D.; Yan, X.; Xiao, X.; Zhang, G.; Wang, Y.; Cao, J.; Ma, R.; Hong, S.; Ma, M. To explore immune synergistic function of Quercetin in inhibiting breast cancer cells. Cancer Cell Int., 2021, 21(1), 632. doi: 10.1186/s12935-021-02345-5 PMID: 34838003
- Wu, Q.; Kroon, P.A.; Shao, H.; Needs, P.W.; Yang, X. Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast-cancer mcf-7 cells. J. Agric. Food Chem., 2018, 66(27), 7181-7189. doi: 10.1021/acs.jafc.8b02420 PMID: 29905475
- Hu, S.; Huang, L.; Meng, L.; Sun, H.; Zhang, W.; Xu, Y. Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogen-activated protein kinase kinase signaling pathways. Mol. Med. Rep., 2015, 12(5), 6745-6751. doi: 10.3892/mmr.2015.4269 PMID: 26502751
- Tan, K.W.; Li, Y.; Paxton, J.W.; Birch, N.P.; Scheepens, A. Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP/ABCG2). Food Chem., 2013, 138(4), 2267-2274. doi: 10.1016/j.foodchem.2012.12.021 PMID: 23497885
- Ashaq, A.; Maqbool, M.F.; Maryam, A.; Khan, M.; Shakir, H.A.; Irfan, M.; Qazi, J.I.; Li, Y.; Ma, T. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytother. Res., 2021, 35(2), 771-789. doi: 10.1002/ptr.6862 PMID: 32945582
- Kim, H.; Lee, J. Hispidulin modulates epithelial mesenchymal transition in breast cancer cells. Oncol. Lett., 2020, 21(2), 155. doi: 10.3892/ol.2020.12416 PMID: 33552273
- Wu, H.T.; Lin, J.; Liu, Y.E.; Chen, H.F.; Hsu, K.W.; Lin, S.H.; Peng, K.Y.; Lin, K.J.; Hsieh, C.C.; Chen, D.R. 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. Phytomedicine, 2021, 81, 153437. doi: 10.1016/j.phymed.2020.153437 PMID: 33352494
- Tsai, K.J.; Tsai, H.Y.; Tsai, C.C.; Chen, T.Y.; Hsieh, T.H.; Chen, C.L.; Mbuyisa, L.; Huang, Y.B.; Lin, M.W. Luteolin inhibits breast cancer stemness and enhances chemosensitivity through the Nrf2-mediated pathway. Molecules, 2021, 26(21), 6452. doi: 10.3390/molecules26216452 PMID: 34770867
- Alkandahri, M.Y.; Pamungkas, B.T.; Oktoba, Z.; Shafirany, M.Z.; Sulastri, L.; Arfania, M.; Anggraeny, E.N.; Pratiwi, A.; Astuti, F.D.; Indriyani; Dewi, S.Y.; Hamidah, S.Z. Hepatoprotective effect of kaempferol: A review of the dietary sources, bioavailability, mechanisms of action, and safety. Adv. Pharmacol. Pharm. Sci., 2023, 2023, 1-16. doi: 10.1155/2023/1387665 PMID: 36891541
- Jan, R.; Khan, M.; Asaf, S.; Lubna; Asif, S.; Kim, K.M. Bioactivity and therapeutic potential of kaempferol and quercetin: New insights for plant and human health. Plants, 2022, 11(19), 2623. doi: 10.3390/plants11192623 PMID: 36235488
- Hinz, N.; Jücker, M. Distinct functions of AKT isoforms in breast cancer: A comprehensive review. Cell Commun. Signal., 2019, 17(1), 154. doi: 10.1186/s12964-019-0450-3 PMID: 31752925
- Duffy, M.J.; Synnott, N.C.; Crown, J. Mutant p53 in breast cancer: Potential as a therapeutic target and biomarker. Breast Cancer Res. Treat., 2018, 170(2), 213-219. doi: 10.1007/s10549-018-4753-7 PMID: 29564741
- Kaur, R.P.; Vasudeva, K.; Kumar, R.; Munshi, A. Role of p53 gene in breast cancer: Focus on mutation spectrum and therapeutic strategies. Curr. Pharm. Des., 2018, 24(30), 3566-3575. doi: 10.2174/1381612824666180926095709 PMID: 30255744
- Annibaldi, A.; Meier, P. Checkpoints in TNF-induced cell death: Implications in inflammation and cancer. Trends Mol. Med., 2018, 24(1), 49-65. doi: 10.1016/j.molmed.2017.11.002 PMID: 29217118
- Cruceriu, D.; Baldasici, O.; Balacescu, O.; Berindan-Neagoe, I. The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: Molecular insights and therapeutic approaches. Cell. Oncol., 2020, 43(1), 1-18. doi: 10.1007/s13402-019-00489-1 PMID: 31900901
- Park, J.H.; Pyun, W.Y.; Park, H.W. Cancer metabolism: Phenotype, signaling and therapeutic targets. Cells, 2020, 9(10), 2308. doi: 10.3390/cells9102308 PMID: 33081387
- Linzer, N.; Trumbull, A.; Nar, R.; Gibbons, M.D.; Yu, D.T.; Strouboulis, J.; Bungert, J. Regulation of RNA Polymerase II transcription initiation and elongation by transcription factor TFII-I. Front. Mol. Biosci., 2021, 8, 681550. doi: 10.3389/fmolb.2021.681550 PMID: 34055891
- Liu, X.; Zhang, Y.; Wang, Y.; Yang, M.; Hong, F.; Yang, S. Protein phosphorylation in cancer: Role of nitric oxide signaling pathway. Biomolecules, 2021, 11(7), 1009. doi: 10.3390/biom11071009 PMID: 34356634
- Holmström, K.M.; Finkel, T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat. Rev. Mol. Cell Biol., 2014, 15(6), 411-421. doi: 10.1038/nrm3801 PMID: 24854789
- Miricescu, D.; Totan, A.; Stanescu-Spinu, I.I.; Badoiu, S.C.; Stefani, C.; Greabu, M. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects. Int. J. Mol. Sci., 2020, 22(1), 173. doi: 10.3390/ijms22010173 PMID: 33375317
- Rahmani, F.; Ferns, G.A.; Talebian, S.; Nourbakhsh, M.; Avan, A.; Shahidsales, S. Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer. Gene, 2020, 737, 144459. doi: 10.1016/j.gene.2020.144459 PMID: 32045660
- Halacli, S.O.; Dogan, A.L. FOXP1 regulation via the PI3K/Akt/p70S6K signaling pathway in breast cancer cells. Oncol. Lett., 2015, 9(3), 1482-1488. doi: 10.3892/ol.2015.2885 PMID: 25663935
- Zhang, T.; Jiang, K.; Zhu, X.; Zhao, G.; Wu, H.; Deng, G.; Qiu, C. miR-433 inhibits breast cancer cell growth via the MAPK signaling pathway by targeting Rap1a. Int. J. Biol. Sci., 2018, 14(6), 622-632. doi: 10.7150/ijbs.24223 PMID: 29904277
- de Heer, E.C.; Jalving, M.; Harris, A.L. HIFs, angiogenesis, and metabolism: Elusive enemies in breast cancer. J. Clin. Invest., 2020, 130(10), 5074-5087. doi: 10.1172/JCI137552 PMID: 32870818
- Zhang, T.; Zhu, X.; Wu, H.; Jiang, K.; Zhao, G.; Shaukat, A.; Deng, G.; Qiu, C. Targeting the ROS/PI3K/AKT/HIF‐1α/HK2 axis of breast cancer cells: Combined administration of Polydatin and 2‐Deoxy‐d‐glucose. J. Cell. Mol. Med., 2019, 23(5), 3711-3723. doi: 10.1111/jcmm.14276 PMID: 30920152
- Ebright, R.Y.; Zachariah, M.A.; Micalizzi, D.S.; Wittner, B.S.; Niederhoffer, K.L.; Nieman, L.T.; Chirn, B.; Wiley, D.F.; Wesley, B.; Shaw, B.; Nieblas-Bedolla, E.; Atlas, L.; Szabolcs, A.; Iafrate, A.J.; Toner, M.; Ting, D.T.; Brastianos, P.K.; Haber, D.A.; Maheswaran, S. HIF1A signaling selectively supports proliferation of breast cancer in the brain. Nat. Commun., 2020, 11(1), 6311. doi: 10.1038/s41467-020-20144-w PMID: 33298946
- Moon, A. Ras Signaling in Breast Cancer. Adv. Exp. Med. Biol., 2021, 1187, 81-101. doi: 10.1007/978-981-32-9620-6_4 PMID: 33983574
- Hussain, M.; Adah, D.; Tariq, M.; Lu, Y.; Zhang, J.; Liu, J. CXCL13/CXCR5 signaling axis in cancer. Life Sci., 2019, 227, 175-186. doi: 10.1016/j.lfs.2019.04.053 PMID: 31026453
- Masjedi, A.; Hashemi, V.; Hojjat-Farsangi, M.; Ghalamfarsa, G.; Azizi, G.; Yousefi, M.; Jadidi-Niaragh, F. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Biomed. Pharmacother., 2018, 108, 1415-1424. doi: 10.1016/j.biopha.2018.09.177 PMID: 30372844
- Siersbæk, R.; Scabia, V.; Nagarajan, S.; Chernukhin, I.; Papachristou, E.K.; Broome, R.; Johnston, S.J.; Joosten, S.E.P.; Green, A.R.; Kumar, S.; Jones, J.; Omarjee, S.; Alvarez-Fernandez, R.; Glont, S.; Aitken, S.J.; Kishore, K.; Cheeseman, D.; Rakha, E.A.; DSantos, C.; Zwart, W.; Russell, A.; Brisken, C.; Carroll, J.S. IL6/STAT3 signaling hijacks estrogen receptor α enhancers to drive breast cancer metastasis. Cancer Cell, 2020, 38(3), 412-423.e9. doi: 10.1016/j.ccell.2020.06.007 PMID: 32679107
- Salgado, E.; Bian, X.; Feng, A.; Shim, H.; Liang, Z. HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206. Biochem. Biophys. Res. Commun., 2018, 503(2), 1087-1091. doi: 10.1016/j.bbrc.2018.06.120 PMID: 29936177
- Du, Y.; Zhang, J.; Meng, Y.; Huang, M.; Yan, W.; Wu, Z. MicroRNA-143 targets MAPK3 to regulate the proliferation and bone metastasis of human breast cancer cells. AMB Express, 2020, 10(1), 134. doi: 10.1186/s13568-020-01072-w PMID: 32737620
- Chen, Z.; Cui, N.; Zhao, J.; Wu, J.; Ma, F.; Li, C.; Liu, X. Expressions of ZNF436, β-catenin, EGFR, and CMTM5 in breast cancer and their clinical significances. Eur. J. Histochem., 2021, 65(1), 3173. doi: 10.4081/ejh.2021.3173 PMID: 33478201
- Williams, C.B.; Phelps-Polirer, K.; Dingle, I.P.; Williams, C.J.; Rhett, M.J.; Eblen, S.T.; Armeson, K.; Hill, E.G.; Yeh, E.S. Correction: HUNK phosphorylates EGFR to regulate breast cancer metastasis. Oncogene, 2021, 40(20), 3635-3636. doi: 10.1038/s41388-021-01797-3 PMID: 33958726
- Zhao, Y.; Ma, J.; Fan, Y.; Wang, Z.; Tian, R.; Ji, W.; Zhang, F.; Niu, R. TGF-β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways. Mol. Oncol., 2018, 12(3), 305-321. doi: 10.1002/1878-0261.12162 PMID: 29215776
- Valenza, C.; Porta, F.M.; Rappa, A.; Guerini-Rocco, E.; viale, G.; Barberis, M.; de Marinis, F.; Curigliano, G.; Catania, C. Complex differential diagnosis between primary breast cancer and breast metastasis from EGFR-mutated lung adenocarcinoma: Case report and literature review. Curr. Oncol., 2021, 28(5), 3384-3392. doi: 10.3390/curroncol28050292 PMID: 34590588
补充文件
