{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:41:02Z","timestamp":1785400862785,"version":"3.56.0"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82373068"],"award-info":[{"award-number":["82373068"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82373068"],"award-info":[{"award-number":["82373068"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Basic Research Program of Jiangsu","award":["BK20250117"],"award-info":[{"award-number":["BK20250117"]}]},{"name":"Young Science and Technology Talents Lifting Project of the Jiangsu Association for Science and Technology","award":["JSTJ-2023-WJ017"],"award-info":[{"award-number":["JSTJ-2023-WJ017"]}]},{"name":"Outstanding Young Scientist Fund of the Nanjing Health Science and Technology Development Program","award":["JQX23005"],"award-info":[{"award-number":["JQX23005"]}]},{"name":"Excellent Young Scientists Fund Cultivation Project of the National Natural Science Foundation of Nanjing Drum Tower Hospital","award":["Nanjing Drum Tower Hospital-2024-JCYJ-YP-04"],"award-info":[{"award-number":["Nanjing Drum Tower Hospital-2024-JCYJ-YP-04"]}]},{"name":"Nanjing Drum Tower Hospital, Affiliated Hospital of the Medical School, Nanjing University","award":["2023-LCYJ-PY-20"],"award-info":[{"award-number":["2023-LCYJ-PY-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Oroxylin A (OA), a natural flavonoid, has demonstrated anticancer potential; nevertheless, its precise molecular targets and mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unclear. To address this gap, we integrated network pharmacology, transcriptomic analysis (GSE101448), and molecular docking, which identified SRC as a core therapeutic target of OA. OA exhibited a strong binding affinity to SRC (\u22129.0 kcal\/mol), and molecular dynamics simulation confirmed stable complex formation (RMSD 0.26 \u00b1 0.02 nm). Combined with functional assays, these findings identify SRC as a critical therapeutic target. Importantly, clinical analysis revealed that SRC was significantly upregulated in PDAC tissues, correlating with poor prognosis. Subsequently, in vitro experiments demonstrated that OA dose-dependently suppressed proliferation, induced G2\/M cell cycle arrest and apoptosis, and inhibited migration and invasion in MIA PaCa-2 and PANC-1 cells. These effects were accompanied by downregulation of MMP2 and MMP9. Mechanistically, OA selectively inhibited phosphorylation of SRC (Tyr416), PI3K, and AKT (Ser473) without altering total protein levels, suggesting that the SRC\/PI3K\/AKT axis is a primary pathway mediating OA\u2019s anticancer activity. Furthermore, in vivo treatment with OA significantly reduced tumor growth in a murine xenograft model without observable toxicity, as indicated by stable body weight, normal organ histology, and unaltered serum liver and kidney function markers. Immunohistochemical analysis further confirmed decreased Ki67 and p-SRC\/p-AKT expression, alongside increased cleaved caspase-3, in OA-treated tumors. Collectively, these findings identify SRC as a direct target of OA and demonstrate that OA suppresses PDAC progression through the inhibition of the SRC\/PI3K\/AKT signaling pathway, thereby supporting its potential as a safe and effective therapeutic candidate for pancreatic cancer.<\/jats:p>","DOI":"10.3390\/biom16050685","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:23:37Z","timestamp":1777987417000},"page":"685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oroxylin A Directly Targets SRC to Inhibit the PI3K\/AKT Signaling Axis in Pancreatic Cancer: An Integrated Bioinformatics and Experimental Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiajun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zujiao","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China"},{"name":"Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.56782\/pps.275","article-title":"Anti-cancer activity of phenyl-1, 3, 5-heptatriyne in human liver cancer","volume":"22","author":"Faridi","year":"2024","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_2","first-page":"205","article-title":"Bioactive potential of non-fermented and fermented Kullakar rice porridge: In vitro evaluation on the therapeutic properties","volume":"23","author":"Sharon","year":"2025","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41575-018-0005-x","article-title":"Therapeutic developments in pancreatic cancer: Current and future perspectives","volume":"15","author":"Neoptolemos","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/jcb.26210","article-title":"Efficacy and Toxicity of Different Chemotherapy Regimens in the Treatment of Advanced or Metastatic Pancreatic Cancer: A Network Meta-Analysis","volume":"119","author":"Liu","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Brugiapaglia, S., Spagnolo, F., and Curcio, C. (2025). Unlocking the Potential of Bioactive Compounds in Pancreatic Cancer Therapy: A Promising Frontier. Biomolecules, 15.","DOI":"10.3390\/biom15050725"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.chroma.2005.03.088","article-title":"Isolation and purification of baicalein, wogonin and oroxylin A from the medicinal plant Scutellaria baicalensis by high-speed counter-current chromatography","volume":"1074","author":"Li","year":"2005","journal-title":"J. Chromatogr. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1021\/np900068t","article-title":"Scuteflorins A and B, dihydropyranocoumarins from Scutellaria lateriflora","volume":"72","author":"Li","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1080\/10286020.2016.1191473","article-title":"5,6-Dihydroxy-3,7,4\u2032-trimethoxyflavonol induces G2\/M cell cycle arrest and apoptosis in human hepatocellular carcinoma cells","volume":"18","author":"Zhao","year":"2016","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1139\/bcb-2014-0030","article-title":"Oroxylin A exerts anti-inflammatory activity on lipopolysaccharide-induced mouse macrophage via Nrf2\/ARE activation","volume":"92","author":"Ye","year":"2014","journal-title":"Biochem. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114761","DOI":"10.1016\/j.bcp.2021.114761","article-title":"Oroxylin A reduces osteoclast formation and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation","volume":"193","author":"Xian","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8891","DOI":"10.2147\/DDDT.S530387","article-title":"Deciphering the Role of Oroxylin A in Liver Fibrosis","volume":"19","author":"Wang","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12225","DOI":"10.1038\/s41598-025-97122-z","article-title":"Oroxylin A may promote cell apoptosis and inhibit epithelial-mesenchymal transition in endometrial cancer, associated with the ER\u03b2\/PI3K\/AKT pathway","volume":"15","author":"Fan","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Gu, K., and Zhou, F. (2023). Dietary Flavonoid Intake and Cancer Mortality: A Population-Based Cohort Study. Nutrients, 15.","DOI":"10.3390\/nu15040976"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103749","DOI":"10.1016\/j.critrevonc.2022.103749","article-title":"Prospects of targeting PI3K\/AKT\/mTOR pathway in pancreatic cancer","volume":"176","author":"Mortazavi","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1158\/2159-8290.CD-24-0177","article-title":"Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer","volume":"14","author":"Dilly","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17588359241284911","DOI":"10.1177\/17588359241284911","article-title":"Inhibition of the PI3K\/AKT\/mTOR pathway in pancreatic cancer: Is it a worthwhile endeavor?","volume":"16","author":"Ouissam","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5546","DOI":"10.1158\/1078-0432.CCR-10-2616","article-title":"Inhibition of SRC family kinases and receptor tyrosine kinases by dasatinib: Possible combinations in solid tumors","volume":"17","author":"Montero","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"119648","DOI":"10.1016\/j.jep.2025.119648","article-title":"Mechanism of ethyl acetate fraction of Amorphophallus konjac against breast cancer based on network pharmacology, molecular docking and experimental validation","volume":"345","author":"Mei","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/bjd\/ljae234","article-title":"Using network pharmacology to discover potential drugs for hypertrophic scars","volume":"191","author":"Zhang","year":"2024","journal-title":"Br. J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111368","DOI":"10.1016\/j.cbi.2024.111368","article-title":"Integrated network pharmacology, bioinformatics, and experiment analysis to decipher the molecular mechanism of Salidroside on Gastric cancer via targeting NCOA4-mediated ferritinophagy","volume":"407","author":"Fu","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s12935-024-03533-9","article-title":"Erianin inhibits the progression of pancreatic cancer by directly targeting AKT and ASK1","volume":"24","author":"Liu","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1111\/jcmm.17787","article-title":"Integration of molecular docking, molecular dynamics and network pharmacology to explore the multi-target pharmacology of fenugreek against diabetes","volume":"27","author":"Luo","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, M., Wang, Y., Deng, W., Xie, J., He, Y., Wang, L., Zhang, J., and Cui, M. (2024). Combining network pharmacology, machine learning, molecular docking and molecular dynamic to explore the mechanism of Chufeng Qingpi decoction in treating schistosomiasis. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1453529"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1038\/s41388-022-02328-4","article-title":"Hesperadin suppresses pancreatic cancer through ATF4\/GADD45A axis at nanomolar concentrations","volume":"41","author":"Zhang","year":"2022","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.7150\/thno.71100","article-title":"PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor","volume":"12","author":"Wang","year":"2022","journal-title":"Theranostics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"120266","DOI":"10.1016\/j.lfs.2021.120266","article-title":"Berberine inhibits gastric cancer development and progression by regulating the JAK2\/STAT3 pathway and downregulating IL-6","volume":"290","author":"Xu","year":"2022","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e7396","DOI":"10.1002\/cam4.7396","article-title":"TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation","volume":"13","author":"Wu","year":"2024","journal-title":"Cancer Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1186\/s12967-022-03582-6","article-title":"MiR-1254 suppresses the proliferation and invasion of cervical cancer cells by modulating CD36","volume":"19","author":"Zhang","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2104793","DOI":"10.1002\/advs.202104793","article-title":"Dynamic Adjust of Non-Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR-II Imaging Mediated Photothermal Therapy and Immunotherapy","volume":"9","author":"Wang","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12943-022-01600-1","article-title":"circEXOC6B interacting with RRAGB, an mTORC1 activator, inhibits the progression of colorectal cancer by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop","volume":"21","author":"Li","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s00259-021-05554-2","article-title":"Fibroblast activation protein targeted therapy using [177Lu]FAPI-46 compared with [225Ac]FAPI-46 in a pancreatic cancer model","volume":"49","author":"Liu","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1186\/s12951-025-03795-z","article-title":"Mitochondrial-targeted photodynamic therapy combined with TGF-\u03b2 inhibition potentiates anti-PD-1 therapy in pancreatic ductal adenocarcinoma","volume":"23","author":"Xu","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1080\/15548627.2022.2093026","article-title":"Autophagy loss impedes cancer-associated fibroblast activation via downregulating proline biosynthesis","volume":"19","author":"Bai","year":"2023","journal-title":"Autophagy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1002\/ptr.8220","article-title":"Curcumin and its anti-colorectal cancer potential: From mechanisms of action to autophagy","volume":"38","author":"Brockmueller","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"106440","DOI":"10.1016\/j.phrs.2022.106440","article-title":"Berberine for gastric cancer prevention and treatment: Multi-step actions on the Correa\u2019s cascade underlie its therapeutic effects","volume":"184","author":"Liu","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jare.2024.02.023","article-title":"Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer","volume":"68","author":"Li","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Han, E.J., Choi, E.Y., Jeon, S.J., Lee, S.W., Moon, J.M., Jung, S.H., and Jung, J.Y. (2023). Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813949"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1111\/jcmm.17246","article-title":"Identification of natural compounds tubercidin and lycorine HCl against small-cell lung cancer and BCAT1 as a therapeutic target","volume":"26","author":"Chen","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127429","DOI":"10.1016\/j.ijbiomac.2023.127429","article-title":"Elucidation of the anti-colon cancer mechanism of Phellinus baumii polyphenol by an integrative approach of network pharmacology and experimental verification","volume":"253","author":"Liu","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"156701","DOI":"10.1016\/j.phymed.2025.156701","article-title":"Kaempferol targets Src to exert its chemopreventive effects on mammary tumorigenesis via regulation of the PI3K\/AKT pathway","volume":"141","author":"Wang","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109313","DOI":"10.1016\/j.jnutbio.2023.109313","article-title":"Lycopene suppresses gastric cancer cell growth without affecting normal gastric epithelial cells","volume":"116","author":"Zhou","year":"2023","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1080\/15548627.2021.2007027","article-title":"CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma","volume":"18","author":"Yao","year":"2022","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1211\/jpp.60.11.0006","article-title":"Oroxylin A induces G2\/M phase cell-cycle arrest via inhibiting Cdk7-mediated expression of Cdc2\/p34 in human gastric carcinoma BGC-823 cells","volume":"60","author":"Yang","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"155688","DOI":"10.1016\/j.phymed.2024.155688","article-title":"Oroxylin A suppresses breast cancer-induced osteoclastogenesis and osteolysis as a natural RON inhibitor","volume":"129","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"24091","DOI":"10.1038\/s41598-024-75457-3","article-title":"Oroxylin A suppressed colorectal cancer metastasis by inhibiting the activation of the TGF-\u03b2\/SMAD signal pathway","volume":"14","author":"Cao","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1038\/onc.2010.589","article-title":"Oncogenic Ras\/Src cooperativity in pancreatic neoplasia","volume":"30","author":"Shields","year":"2011","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Carusillo, A., and Mussolino, C. (2020). DNA Damage: From Threat to Treatment. Cells, 9.","DOI":"10.3390\/cells9071665"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s12253-016-0106-1","article-title":"Oroxylin a could be a Promising Radiosensitizer for Esophageal Squamous Cell Carcinoma by Inducing G2\/M Arrest and Activating Apoptosis","volume":"23","author":"Tan","year":"2017","journal-title":"Pathol. Oncol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9241769","DOI":"10.1155\/2019\/9241769","article-title":"Oroxylin A Suppresses the Cell Proliferation, Migration, and EMT via NF-\u03baB Signaling Pathway in Human Breast Cancer Cells","volume":"2019","author":"Sun","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41575-020-0300-1","article-title":"Pancreatic cancer stroma: An update on therapeutic targeting strategies","volume":"17","author":"Hosein","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"BSR20190159","DOI":"10.1042\/BSR20190159","article-title":"Isorhamnetin inhibited migration and invasion via suppression of Akt\/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells","volume":"39","author":"Luo","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"112362","DOI":"10.1016\/j.intimp.2024.112362","article-title":"Targeting TRIM40 signaling reduces esophagus cancer development: A mechanism involving in protection of oroxylin A","volume":"137","author":"Ji","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/j.drudis.2014.08.006","article-title":"Multi-target approach for natural products in inflammation","volume":"19","author":"Koeberle","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.2174\/1381612826666200128095248","article-title":"Flavonoids as Multi-Target Compounds: A Special Emphasis on their Potential as Chemo-adjuvants in Cancer Therapy","volume":"26","author":"Namdeo","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zeng, S., P\u00f6ttler, M., Lan, B., Gr\u00fctzmann, R., Pilarsky, C., and Yang, H. (2019). Chemoresistance in Pancreatic Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184504"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12964-025-02174-3","article-title":"Reversal of epithelial to mesenchymal transition in triple negative breast cancer through epigenetic modulations by dietary flavonoid Galangin and its combination with SAHA","volume":"23","author":"Nimal","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_57","first-page":"801","article-title":"First-in-class drug oroxylin A tablets for treating hepatic and gastrointestinal disorders: From preclinical development to clinical research","volume":"23","author":"Luo","year":"2025","journal-title":"Chin. J. Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2008.12.008","article-title":"Oroxylin A suppresses invasion through down-regulating the expression of matrix metalloproteinase-2\/9 in MDA-MB-435 human breast cancer cells","volume":"603","author":"Sun","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/jcp.24833","article-title":"UCP2-related mitochondrial pathway participates in oroxylin A-induced apoptosis in human colon cancer cells","volume":"230","author":"Qiao","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e1714","DOI":"10.1038\/cddis.2015.86","article-title":"Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1\u03b1 destabilization","volume":"6","author":"Wei","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/jmv.25337","article-title":"Oroxylin A inhibits Kaposi\u2019s sarcoma-associated herpes virus (KSHV) vIL-6-mediated lymphatic reprogramming of vascular endothelial cells through modulating PPAR\u03b3\/Prox1 axis","volume":"91","author":"Zhu","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/carcin\/bgy004","article-title":"Oroxylin A, a natural compound, mitigates the negative effects of TNF\u03b1-treated acute myelogenous leukemia cells","volume":"39","author":"Li","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Costamagna, A., Milan, G., De Santis, M.C., Carrer, A., and Martini, M. (Trends Endocrinol. Metab., 2026). Lipid signaling networks in pancreatic cancer progression and therapeutic perspectives, Trends Endocrinol. Metab., in press.","DOI":"10.1016\/j.tem.2026.03.004"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"151769","DOI":"10.1016\/j.acthis.2021.151769","article-title":"The enhancement of Tetrandrine to gemcitabine-resistant PANC-1 cytochemical sensitivity involves the promotion of PI3K\/Akt\/mTOR-mediated apoptosis and AMPK-regulated autophagy","volume":"123","author":"Song","year":"2021","journal-title":"Acta Histochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.2741\/4037","article-title":"Src-mediated regulation of E-cadherin and EMT in pancreatic cancer","volume":"17","author":"Nagathihalli","year":"2012","journal-title":"Front. Biosci. (Landmark Ed.)"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/685\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:25:27Z","timestamp":1778127927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050685"],"URL":"https:\/\/doi.org\/10.3390\/biom16050685","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}