{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:09:33Z","timestamp":1785413373797,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cTianshan Talents\u201d\u2014Science and Technology Innovation Leading Talents Training Project"},{"name":"Department of Science and Technology of the Xinjiang Uyghur Autonomous Region and the Science and Technology Bureau of the Xinjiang Production and Construction Corps","award":["2023TSYCLJ0057"],"award-info":[{"award-number":["2023TSYCLJ0057"]}]},{"award":["2023TSYCLJ0057"],"award-info":[{"award-number":["2023TSYCLJ0057"]}],"id":[{"id":"https:\/\/ror.org\/03hcmxw73","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Observation and Application of the Therapeutic Effect of Traditional Chinese Medicine Prescriptions from Authentic Medicinal Materials in Xinjiang in the Treatment of Burns and Scalds","award":["2024RC012"],"award-info":[{"award-number":["2024RC012"]}]},{"name":"Treatment of Burns and Scalds and Promotion of Full-Functional Skin Reconstruction Using Traditional Chinese Medicine Prescriptions from Characteristic Plants in Southern Xinjiang","award":["2024ZR-009"],"award-info":[{"award-number":["2024ZR-009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Bladder cancer (BC) remains a major clinical challenge owing to limited therapeutic options and high recurrence rates. Oridonin (ORI), a natural diterpenoid derived from Rabdosia plants, exhibits promising anti-tumor activity, but its effects and mechanisms in BC remain poorly defined. We evaluated the anti-BC potential of ORI in vitro and in vivo using proliferation, migration, invasion, cell-cycle, and apoptosis assays, integrated transcriptomic and proteomic analyses, Western blotting, and a 5637 xenograft model. ORI dose- and time-dependently inhibited 5637 and T24 cell proliferation, induced S-phase arrest (from 23.37% to 42.12% in 5637 and from 31.87% to 50.28% in T24; p &lt; 0.01), and reduced migration (from 53.39% to 13.77% and from 59.81% to 12.49%; p &lt; 0.0001) and invasion (from 74.42% to 25.43% and from 67.03% to 30.12%; p &lt; 0.001). Multi-omics analyses revealed widespread changes enriched in apoptosis- and cell-cycle-related pathways. Consistently, ORI promoted apoptosis and necrosis, up-regulating BAX, CASP3, BID, and CYCS and down-regulating BCL2, validating the omics findings. In vivo, ORI (20 mg\/kg, daily gavage) significantly suppressed xenograft growth (p &lt; 0.001) without obvious toxicity, indicating that ORI inhibits BC growth and metastasis by inducing S-phase arrest and apoptosis and is a promising candidate for BC therapy.<\/jats:p>","DOI":"10.3390\/ijms27156835","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:54Z","timestamp":1785411534000},"page":"6835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oridonin Suppresses Bladder Cancer Growth and Metastasis by Inducing S-Phase Arrest and Apoptosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Wenqiang","family":"Sun","sequence":"first","affiliation":[{"name":"The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2016-1824","authenticated-orcid":false,"given":"Yongchao","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglong","family":"Xu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haocheng","family":"Guan","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghui","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dobruch, J., and Oszczud\u0142owski, M. (2021). Bladder cancer: Current challenges and future directions. Medicina, 57.","DOI":"10.3390\/medicina57080749"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/14737159.2020.1699791","article-title":"Current and emerging bladder cancer biomarkers with an emphasis on urine biomarkers","volume":"20","author":"Cheng","year":"2020","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/bmb\/ldy034","article-title":"The latest treatment options for bladder cancer","volume":"128","author":"Crabb","year":"2018","journal-title":"Br. Med. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s11255-022-03173-w","article-title":"Cigarette smoking and risk of bladder cancer: A dose\u2013response meta-analysis","volume":"54","author":"Zhao","year":"2022","journal-title":"Int. Urol. Nephrol."},{"key":"ref_6","first-page":"1417","article-title":"Prospects and progress of immunotherapy for bladder cancer","volume":"17","author":"Boegemann","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, M., Zhang, Z., Li, Z., Zhu, Y., and Xu, C. (2023). E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1226057"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gill, E., and Perks, C.M. (2024). Mini-review: Current bladder cancer treatment\u2014The need for improvement. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031557"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xu, J., Wold, E.A., Ding, Y., Shen, Q., and Zhou, J. (2018). Therapeutic potential of oridonin and its analogs: From anticancer and anti-inflammation to neuroprotection. Molecules, 23.","DOI":"10.3390\/molecules23020474"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.2174\/0109298673273034231215190811","article-title":"Research and development progression of oridonin for hematological malignancies therapy","volume":"32","author":"Feng","year":"2025","journal-title":"Curr. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2174\/1389557517666170417170609","article-title":"Recent development of oridonin derivatives with diverse pharmacological activities","volume":"19","author":"Cheng","year":"2019","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119200","DOI":"10.1016\/j.jep.2024.119200","article-title":"Rabdosia rubescens (Hemsl.) H. Hara: A potent anti-tumor herbal remedy\u2014Botany, phytochemistry, and clinical applications and insights","volume":"340","author":"Gao","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1038\/s41467-018-04947-6","article-title":"Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity","volume":"9","author":"He","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lin, J., Lai, X., Fan, X., Ye, B., Zhong, L., Zhang, Y., Shao, R., Shi, S., Huang, W., and Su, L. (2022). Oridonin protects against myocardial ischemia\u2013reperfusion injury by inhibiting GSDMD-mediated pyroptosis. Genes, 13.","DOI":"10.3390\/genes13112133"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112419","DOI":"10.1016\/j.mce.2024.112419","article-title":"Oridonin attenuates diabetic retinopathy progression by suppressing the NLRP3 inflammasome pathway","volume":"596","author":"Zhang","year":"2025","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3002962","DOI":"10.1155\/2022\/3002962","article-title":"Oridonin attenuates cisplatin-induced acute kidney injury via inhibiting oxidative stress, apoptosis, and inflammation in mice","volume":"2022","author":"Gu","year":"2022","journal-title":"BioMed Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"655","DOI":"10.2174\/1389201024666230821110116","article-title":"The natural product oridonin as an anticancer agent: Current achievements and problems","volume":"25","author":"Hu","year":"2024","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1002\/fsn3.3986","article-title":"Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy\u2014A comprehensive review","volume":"12","author":"Ali","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, D., Han, T., Liao, J., Hu, X., Xu, S., Tian, K., Gu, X., Cheng, K., Li, Z., and Hua, H. (2016). Oridonin, a promising ent-kaurane diterpenoid lead compound. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091395"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sobral, P.J.M., Vicente, A.T.S., and Salvador, J.A.R. (2023). Recent advances in oridonin derivatives with anticancer activity. Front. Chem., 11.","DOI":"10.3389\/fchem.2023.1066280"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.2147\/CMAR.S271759","article-title":"Oridonin induces apoptosis of laryngeal carcinoma via endoplasmic reticulum stress","volume":"12","author":"Kou","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1111\/jcmm.17841","article-title":"Oridonin suppresses gastric cancer SGC-7901 cell proliferation by targeting the TNF-\u03b1\/androgen receptor\/TGF-\u03b2 signalling pathway axis","volume":"27","author":"Gao","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.14715\/cmb\/2024.70.6.17","article-title":"Oridonin represses lung cancer cell proliferation and migration by modulating AFAP1-AS1\/IGF2BP1","volume":"70","author":"Chen","year":"2024","journal-title":"Cell. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155426","DOI":"10.1016\/j.phymed.2024.155426","article-title":"Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1","volume":"126","author":"Liu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"965","DOI":"10.7150\/ijms.70733","article-title":"Oridonin represses epithelial\u2013mesenchymal transition and angiogenesis of thyroid cancer via downregulating JAK2\/STAT3 signaling","volume":"19","author":"Liu","year":"2022","journal-title":"Int. J. Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.1002\/jcb.27654","article-title":"Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K\/AKT\/mTOR and Ras\/Raf pathways","volume":"120","author":"Jiang","year":"2019","journal-title":"J. Cell. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:40:20Z","timestamp":1785411620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":26,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156835"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156835","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}