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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Glioblastoma is the most aggressive primary malignant brain tumor of the central nervous system and remains difficult to treat because of rapid progression, diffuse invasion, and frequent recurrence. This study aimed to identify a potential natural compound against glioblastoma using a reverse network pharmacology strategy and to investigate its anti-glioma effects and underlying mechanism.Methods:Glioblastoma-related targets were collected from public disease databases and integrated with differentially expressed genes from a public transcriptomic dataset to identify intersecting targets. Protein-protein interaction analysis, hub target screening, functional enrichment analysis, and reverse network pharmacology were performed to identify candidate compounds. Molecular docking and 100-ns molecular dynamics simulations were used to assess interactions between 20-hydroxyecdysone and pathway-related targets. Cell viability, colony formation, apoptosis, migration, and protein expression were examined in U251 and U87 glioma cells. Statistical differences were analyzed using a paired Student\u2019s t-test for two-group comparisons or one-way analysis of variance (ANOVA) followed by Dunnett\u2019s multiple-comparisons test for multi-group comparisons, as appropriate.Results:A total of 136 intersecting targets and 18 hub targets were identified. Functional enrichment analysis indicated that the phosphatidylinositol 3-kinase\/protein kinase B signaling pathway was one of the key enriched pathways. Reverse network pharmacology identified 20-hydroxyecdysone as a candidate compound. Molecular docking showed relatively strong binding of 20-hydroxyecdysone to epidermal growth factor receptor, fms-related receptor tyrosine kinase 1, and integrin subunit alpha 5, and molecular dynamics simulations supported the stability of these complexes. In vitro experiments showed that 20-hydroxyecdysone inhibited cell viability, clonogenicity, and migration, while promoting apoptosis. It also reduced the phosphorylation levels of phosphatidylinositol 3-kinase, protein kinase B, and glycogen synthase kinase 3 beta at Ser9 without markedly altering total protein expression.Conclusion:Treatment with 20-Hydroxyecdysone showed anti-glioma activity in vitro and may exert its effects, at least in part, through suppression of the phosphatidylinositol 3-kinase\/protein kinase B signaling pathway. These findings support its further evaluation as a potential therapeutic candidate for glioblastoma.<\/jats:p>","DOI":"10.31083\/fbl52978","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["Reverse Network Pharmacology\u2013Based Identification of 20-Hydroxyecdysone and Its Inhibition of Glioblastoma Malignant Phenotypes Through the PI3K\/AKT Pathway"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6726-8788","authenticated-orcid":true,"given":"Jinhui","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Translational Medicine Research Center, Guizhou Biomanufacturing Laboratory, Guizhou Medical University, 561113 Guiyang, Guizhou, China"},{"name":"Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0046-4307","authenticated-orcid":true,"given":"Chao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-5807","authenticated-orcid":true,"given":"Dongyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6247-9461","authenticated-orcid":true,"given":"Renmi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7773-6423","authenticated-orcid":true,"given":"Xiangdan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0116-9969","authenticated-orcid":true,"given":"Jianwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Translational Medicine Research Center, Guizhou Biomanufacturing Laboratory, Guizhou Medical University, 561113 Guiyang, Guizhou, China"},{"name":"Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-0240","authenticated-orcid":true,"given":"Junhou","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Tissue Engineering and Stem Cell Research, Translational Medicine Research Center, Guizhou Biomanufacturing Laboratory, Guizhou Medical University, 561113 Guiyang, Guizhou, China"},{"name":"Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Price M, Ballard CAP, Benedetti JR, Kruchko C, Barnholtz-Sloan JS, Ostrom QT. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2018-2022. Neuro-Oncology. 2025; 27: iv1\u2013iv66.","DOI":"10.1093\/neuonc\/noaf194"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology. 2021; 23: 1231\u20131251.","DOI":"10.1093\/neuonc\/noab106"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England Journal of Medicine. 2005; 352: 987\u2013996.","DOI":"10.1056\/NEJMoa043330"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Vaz-Salgado MA, Villamayor M, Albarr\u00e1n V, Al\u00eda V, Sotoca P, Chamorro J, et al. Recurrent Glioblastoma: A Review of the Treatment Options. Cancers. 2023; 15: 4279.","DOI":"10.3390\/cancers15174279"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Sharma P, Aaroe A, Liang J, Puduvalli VK. Tumor microenvironment in glioblastoma: Current and emerging concepts. Neuro-Oncology Advances. 2023; 5: vdad009.","DOI":"10.1093\/noajnl\/vdad009"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Newman DJ, Cragg GM. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019. Journal of Natural Products. 2020; 83: 770\u2013803.","DOI":"10.1021\/acs.jnatprod.9b01285"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Hopkins AL. Network pharmacology. Nature Biotechnology. 2007; 25: 1110\u20131111.","DOI":"10.1038\/nbt1007-1110"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nature Chemical Biology. 2008; 4: 682\u2013690.","DOI":"10.1038\/nchembio.118"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Chandran U, Mehendale N, Patil S, Chaguturu R, Patwardhan B. Network Pharmacology. In Patwardhan B, Chaguturu R (eds.) Innovative Approaches in Drug Discovery (pp. 127\u2013164). Academic Press: Boston. 2017.","DOI":"10.1016\/B978-0-12-801814-9.00005-2"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Kong X, Liu C, Zhang Z, Cheng M, Mei Z, Li X, et al. BATMAN-TCM 2.0: an enhanced integrative database for known and predicted interactions between traditional Chinese medicine ingredients and target proteins. Nucleic Acids Research. 2024; 52: D1110\u2013D1120.","DOI":"10.1093\/nar\/gkad926"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Dinan L, Dioh W, Veillet S, Lafont R. 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases. Biomedicines. 2021; 9: 492.","DOI":"10.3390\/biomedicines9050492"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Shuvalov O, Kirdeeva Y, Fefilova E, Netsvetay S, Zorin M, Vlasova Y, et al. 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells. Metabolites. 2023; 13: 656.","DOI":"10.3390\/metabo13050656"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Ma Q, Wu F, Liu X, Zhao C, Sun Y, Li Y, et al. 20-hydroxyecdysone suppresses bladder cancer progression via inhibiting USP21: A mechanism associated with deubiquitination and degradation of p65. Translational Oncology. 2024; 45: 101958.","DOI":"10.1016\/j.tranon.2024.101958"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Martins A, Sipos P, D\u00e9r K, Cs\u00e1bi J, Miklos W, Berger W, et al. Ecdysteroids sensitize MDR and non-MDR cancer cell lines to doxorubicin, paclitaxel, and vincristine but tend to protect them from cisplatin. BioMed Research International. 2015; 2015: 895360.","DOI":"10.1155\/2015\/895360"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Majewska E, Szeliga M. AKT\/GSK3\u03b2 Signaling in Glioblastoma. Neurochemical Research. 2017; 42: 918\u2013924.","DOI":"10.1007\/s11064-016-2044-4"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Chikano Y, Domoto T, Furuta T, Sabit H, Kitano-Tamura A, Pyko IV, et al. Glycogen synthase kinase 3\u03b2 sustains invasion of glioblastoma via the focal adhesion kinase, Rac1, and c-Jun N-terminal kinase-mediated pathway. Molecular Cancer Therapeutics. 2015; 14: 564\u2013574.","DOI":"10.1158\/1535-7163.MCT-14-0479"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Minegishi K, Dobashi Y, Kimura E, Goto A. AKT: A Central Node in Complex Signaling Cascades. Frontiers in Bioscience (Landmark Edition). 2025; 30: 26414.","DOI":"10.31083\/fbl26414"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Zhao B, Shen C, Zheng Z, Wang X, Zhao W, Chen X, et al. Peiminine Inhibits Glioblastoma in Vitro and in Vivo Through Cell Cycle Arrest and Autophagic Flux Blocking. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2018; 51: 1566\u20131583.","DOI":"10.1159\/000495646"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Carrillo-Beltr\u00e1n D, Nahuelpan Y, Cuevas C, Fabres K, Silva P, Zubieta J, et al. Glycosylated Delphinidins Decrease Chemoresistance to Temozolomide by Regulating NF-\u03baB\/MGMT Signaling in Glioblastoma. Cells. 2025; 14: 179.","DOI":"10.3390\/cells14030179"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Dioh W, Tourette C, Del Signore S, Daudigny L, Dupont P, Balducci C, et al. A Phase 1 study for safety and pharmacokinetics of BIO101 (20-hydroxyecdysone) in healthy young and older adults. Journal of Cachexia, Sarcopenia and Muscle. 2023; 14: 1259\u20131273.","DOI":"10.1002\/jcsm.13195"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Romaniuk-Drapa\u0142a A, Lisiak N, Toto\u0144 E, Matysiak A, Nawrot J, Nowak G, et al. Proapoptotic and proautophagic activity of 20-hydroxyecdysone in breast cancer cells in vitro. Chemico-Biological Interactions. 2021; 342: 109479.","DOI":"10.1016\/j.cbi.2021.109479"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Singh S, Dey D, Barik D, Mohapatra I, Kim S, Sharma M, et al. Glioblastoma at the crossroads: current understanding and future therapeutic horizons. Signal Transduction and Targeted Therapy. 2025; 10: 213.","DOI":"10.1038\/s41392-025-02299-4"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Shetty C, Tamatta R, Dhas N, Singh AK. Evolving therapeutic strategies in glioblastoma: traditional approaches and novel interventions. 3 Biotech. 2025; 15: 318.","DOI":"10.1007\/s13205-025-04493-1"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Kurdi M, Bamaga A, Alkhotani A, Alsharif T, Abdel-Hamid GA, Selim ME, et al. Mitochondrial DNA Alterations in Glioblastoma and Current Therapeutic Targets. Frontiers in Bioscience (Landmark Edition). 2024; 29: 367.","DOI":"10.31083\/j.fbl2910367"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Barab\u00e1si AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nature Reviews. Genetics. 2011; 12: 56\u201368.","DOI":"10.1038\/nrg2918"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, Schmidt HHHW. Network pharmacology: curing causal mechanisms instead of treating symptoms. Trends in Pharmacological Sciences. 2022; 43: 136\u2013150.","DOI":"10.1016\/j.tips.2021.11.004"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Lagunin AA, Ivanov SM, Gloriozova TA, Pogodin PV, Filimonov DA, Kumar S, et al. Combined network pharmacology and virtual reverse pharmacology approaches for identification of potential targets to treat vascular dementia. Scientific Reports. 2020; 10: 257.","DOI":"10.1038\/s41598-019-57199-9"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Qin A, Musket A, Musich PR, Schweitzer JB, Xie Q. Receptor tyrosine kinases as druggable targets in glioblastoma: Do signaling pathways matter? Neuro-Oncology Advances. 2021; 3: vdab133.","DOI":"10.1093\/noajnl\/vdab133"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Manning BD, Toker A. AKT\/PKB Signaling: Navigating the Network. Cell. 2017; 169: 381\u2013405.","DOI":"10.1016\/j.cell.2017.04.001"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Joy AM, Beaudry CE, Tran NL, Ponce FA, Holz DR, Demuth T, et al. Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. Journal of Cell Science. 2003; 116: 4409\u20134417.","DOI":"10.1242\/jcs.00712"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Ezzati S, Salib S, Balasubramaniam M, Aboud O. Epidermal Growth Factor Receptor Inhibitors in Glioblastoma: Current Status and Future Possibilities. International Journal of Molecular Sciences. 2024; 25: 2316.","DOI":"10.3390\/ijms25042316"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Shi Y, Wu M, Liu Y, Hu L, Wu H, Xie L, et al. ITGA5 Predicts Dual-Drug Resistance to Temozolomide and Bevacizumab in Glioma. Frontiers in Oncology. 2021; 11: 769592.","DOI":"10.3389\/fonc.2021.769592"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Feng L, Ma J, Ji H, Liu Y, Hu W. miR-330-5p suppresses glioblastoma cell proliferation and invasiveness by targeting ITGA5. Oncology Reports. 2017; 38: 1749\u20131757.","DOI":"10.3892\/or.2017.5827"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Peterson TE, Kirkpatrick ND, Huang Y, Farrar CT, Marijt KA, Kloepper J, et al. Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113: 4470\u20134475.","DOI":"10.1073\/pnas.1525349113"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Cescon M, Rampazzo E, Bresolin S, Da Ros F, Manfreda L, Cani A, et al. Collagen VI sustains cell stemness and chemotherapy resistance in glioblastoma. Cellular and Molecular Life Sciences: CMLS. 2023; 80: 233.","DOI":"10.1007\/s00018-023-04887-5"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Zaj\u0105c A, Sumorek-Wiadro J, Langner E, Wertel I, Maciejczyk A, Pawlikowska-Pawl\u0119ga B, et al. Involvement of PI3K Pathway in Glioma Cell Resistance to Temozolomide Treatment. International Journal of Molecular Sciences. 2021; 22: 5155.","DOI":"10.3390\/ijms22105155"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Zhang H, Liu Z, Cheng J, Jiang Y, Zheng X, Zhang C, et al. HTR1D regulates the PI3K\/Akt signaling pathway to impact glioblastoma development and resistance to temozolomide. Chemico-biological Interactions. 2025; 421: 111748.","DOI":"10.1016\/j.cbi.2025.111748"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Domoto T, Uehara M, Bolidong D, Minamoto T. Glycogen Synthase Kinase 3\u03b2 in Cancer Biology and Treatment. Cells. 2020; 9: 1388.","DOI":"10.3390\/cells9061388"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Yang W, Wu PF, Ma JX, Liao MJ, Wang XH, Xu LS, et al. Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3\u03b2\/\u03b2-catenin\/twist pathway. Cell Death & Disease. 2019; 10: 208.","DOI":"10.1038\/s41419-019-1449-9"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Zhang X, Zheng K, Li C, Zhao Y, Li H, Liu X, et al. Nobiletin inhibits invasion via inhibiting AKT\/GSK3\u03b2\/\u03b2-catenin signaling pathway in Slug-expressing glioma cells. Oncology Reports. 2017; 37: 2847\u20132856.","DOI":"10.3892\/or.2017.5522"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Chen YC. Beware of docking! Trends in Pharmacological Sciences. 2015; 36: 78\u201395.","DOI":"10.1016\/j.tips.2014.12.001"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Hollingsworth SA, Dror RO. Molecular Dynamics Simulation for All. Neuron. 2018; 99: 1129\u20131143.","DOI":"10.1016\/j.neuron.2018.08.011"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Martinez Molina D, Jafari R, Ignatushchenko M, Seki T, Larsson EA, Dan C, et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science (New York, N.Y.). 2013; 341: 84\u201387.","DOI":"10.1126\/science.1233606"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Jafari R, Almqvist H, Axelsson H, Ignatushchenko M, Lundb\u00e4ck T, Nordlund P, et al. The cellular thermal shift assay for evaluating drug target interactions in cells. Nature Protocols. 2014; 9: 2100\u20132122.","DOI":"10.1038\/nprot.2014.138"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: Good news and bad news. Science Translational Medicine. 2016; 8: 354re3.","DOI":"10.1126\/scitranslmed.aaf6853"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Torsvik A, Stieber D, Enger P\u00d8, Golebiewska A, Molven A, Svendsen A, et al. U-251 revisited: genetic drift and phenotypic consequences of long-term cultures of glioblastoma cells. Cancer Medicine. 2014; 3: 812\u2013824.","DOI":"10.1002\/cam4.219"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Logun M, Wang X, Sun Y, Bagley SJ, Li N, Desai A, et al. Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy. Cell Stem Cell. 2025; 32: 181\u2013190.e4.","DOI":"10.1016\/j.stem.2024.11.010"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Z\u00e1dor E. Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? Cells. 2025; 14: 431.","DOI":"10.3390\/cells14060431"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Rahman MA, Jalouli M, Yadab MK, Al-Zharani M. Progress in Drug Delivery Systems Based on Nanoparticles for Improved Glioblastoma Therapy: Addressing Challenges and Investigating Opportunities. 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