{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:19:29Z","timestamp":1791299969301,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T00:00:00Z","timestamp":1482105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81460460"],"award-info":[{"award-number":["81460460"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-\u03baB p65, Bcl-2 and VEGF proteins without affecting other NF-\u03baB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-\u03baB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC.<\/jats:p>","DOI":"10.3390\/ijms17122139","type":"journal-article","created":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T04:09:09Z","timestamp":1482466149000},"page":"2139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-\u03baB-Related Mechanism"],"prefix":"10.3390","volume":"17","author":[{"given":"Weiying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyin","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rensheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.tim.2004.06.005","article-title":"Ebv-associated nasopharyngeal carcinomas: From epidemiology to virus-targeting strategies","volume":"12","author":"Busson","year":"2004","journal-title":"Trends Microbiol."},{"key":"ref_2","first-page":"731","article-title":"Primary noncutaneous melanoma","volume":"20","author":"Wu","year":"2000","journal-title":"Clin. Lab. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3892\/ol.2012.1063","article-title":"Anticancer effects of 3,3\u2032-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells","volume":"5","author":"Xu","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1002\/cncr.25754","article-title":"Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: Long-term results of a phase 2 study","volume":"117","author":"Xiao","year":"2011","journal-title":"Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhuang, M., Zhao, M., Qiu, H., Shi, D., Wang, J., Tian, Y., Lin, L., and Deng, W. (2014). Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting Nf-\u03baB and COX-2 signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109951"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1158\/0008-5472.CAN-06-2472","article-title":"Tumor-suppressive effect of retinoid receptor-induced gene-1 (RRIG1) in esophageal cancer","volume":"67","author":"Huang","year":"2007","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.phymed.2009.03.021","article-title":"Effects of triptolide from Tripterygium wilfordii on ER\u03b1 and p53 expression in two human breast cancer cell lines","volume":"16","author":"Liu","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jep.2014.06.006","article-title":"Triptolide: Progress on research in pharmacodynamics and toxicology","volume":"155","author":"Li","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.3892\/or.2014.3115","article-title":"Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells","volume":"31","author":"Li","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_10","first-page":"979","article-title":"Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells","volume":"25","author":"Li","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_11","first-page":"1397","article-title":"Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-\u03baB-related mechanism","volume":"22","author":"Zhu","year":"2009","journal-title":"Oncol. Rep."},{"key":"ref_12","first-page":"65","article-title":"Triptolide inhibits the growth and metastasis of solid tumors","volume":"2","author":"Yang","year":"2003","journal-title":"Mol. Cancer Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/pgmj.2006.055426","article-title":"Synergistic effect of triptolide combined with 5-fluorouracil on colon carcinoma","volume":"83","author":"Tang","year":"2007","journal-title":"Postgrad. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.exphem.2008.08.002","article-title":"Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells","volume":"36","author":"Pigneux","year":"2008","journal-title":"Exp. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.canlet.2014.03.016","article-title":"Triptolide sensitizes pancreatic cancer cells to trail-induced activation of the death receptor pathway","volume":"348","author":"Chen","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1158\/1078-0432.CCR-07-0416","article-title":"Enhanced antitumor effect of combined triptolide and ionizing radiation","volume":"13","author":"Wang","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_17","first-page":"341","article-title":"Nuclear transcription factor NF-\u03baB: Role in biology and medicine","volume":"42","author":"Aggarwal","year":"2004","journal-title":"Indian J. Exp. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1159\/000113491","article-title":"Expression of tyrosine kinase Etk\/Bmx and its relationship with AP-1- and NF-\u03baB-associated proteins in hepatocellular carcinoma","volume":"72","author":"Guo","year":"2007","journal-title":"Oncology"},{"key":"ref_19","first-page":"70","article-title":"Expression of NF-\u03baB and COX-2 in young versus older patients with sporadic colorectal cancer","volume":"41","author":"Abdullah","year":"2009","journal-title":"Acta Med. Indones."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1002\/cncr.25190","article-title":"Nuclear factor \u03baB transcription factors are coexpressed and convey a poor outcome in ovarian cancer","volume":"116","author":"Annunziata","year":"2010","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ccr.2007.07.003","article-title":"Promiscuous mutations activate the noncanonical NF-\u03baB pathway in multiple myeloma","volume":"12","author":"Keats","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1471-2407-8-41","article-title":"NF-\u03baB genes have a major role in inflammatory breast cancer","volume":"8","author":"Lerebours","year":"2008","journal-title":"BMC Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00428-007-0396-5","article-title":"Expression of nuclear factor \u03baB in human gastric carcinoma: Relationship with I\u03baB a and prognostic significance","volume":"450","author":"Levidou","year":"2007","journal-title":"Virchows Arch."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1097\/00005537-200405000-00012","article-title":"Epstein-Barr virus (EBV) latent membrane protein 1 induces interleukin-8 through the nuclear factor-\u03baB signaling pathway in EBV-infected nasopharyngeal carcinoma cell line","volume":"114","author":"Ren","year":"2004","journal-title":"Laryngoscope"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1593\/neo.05625","article-title":"Epstein-Barr virus infection alters cellular signal cascades in human nasopharyngeal epithelial cells","volume":"8","author":"Lo","year":"2006","journal-title":"Neoplasia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8390","DOI":"10.1073\/pnas.1101747108","article-title":"Cysteine-rich intestinal protein 2 (CRIP2) acts as a repressor of NF-\u03baB-mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis","volume":"108","author":"Cheung","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1093\/carcin\/bgs027","article-title":"Id-1 and the p65 subunit of NF-\u03baB promote migration of nasopharyngeal carcinoma cells and are correlated with poor prognosis","volume":"33","author":"Sun","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/35025220","article-title":"Angiogenesis in cancer and other diseases","volume":"407","author":"Carmeliet","year":"2000","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1152\/physrev.00024.2002","article-title":"Clinical, cellular, and molecular aspects of cancer invasion","volume":"83","author":"Mareel","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1200\/JCO.2005.06.081","article-title":"Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis","volume":"23","author":"Hicklin","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jhep.2004.04.035","article-title":"Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): A novel mechanism for tumor invasion","volume":"41","author":"Schmitt","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1083\/jcb.200408130","article-title":"Endothelial barrier disruption by VEGF-mediated SRC activity potentiates tumor cell extravasation and metastasis","volume":"167","author":"Weis","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25176","DOI":"10.1074\/jbc.272.40.25176","article-title":"Genomic organization of human and mouse genes for vascular endothelial growth factor C","volume":"272","author":"Chilov","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1124\/mol.108.052605","article-title":"A small-molecule triptolide suppresses angiogenesis and invasion of human anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor-\u03baB pathway","volume":"75","author":"Zhu","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1002\/ijc.28583","article-title":"Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by NF-\u03baB downregulation","volume":"134","author":"Liu","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.phytochem.2006.11.029","article-title":"Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)","volume":"68","author":"Brinker","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1074\/jbc.M009713200","article-title":"Triptolide and chemotherapy cooperate in tumor cell apoptosis. A role for the p53 pathway","volume":"276","author":"Chang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"195","DOI":"10.14712\/fb2015061050195","article-title":"Triptolide induces apoptosis and synergizes with cisplatin in cisplatin-resistant HNE1\/DDP nasopharyngeal cancer cells","volume":"61","author":"Wang","year":"2015","journal-title":"Folia Biol. (Praha)"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1055\/s-0033-1360315","article-title":"Enhanced anti-tumor activity of triptolide in combination with irradiation for the treatment of oral cancer","volume":"80","author":"Chen","year":"2014","journal-title":"Planta Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1126\/science.275.5303.1129","article-title":"Prevention of apoptosis by BCL-2: Release of cytochrome c from mitochondria blocked","volume":"275","author":"Yang","year":"1997","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1359-6446(03)02670-9","article-title":"Anti-angiogenesis: Biology is the foundation for therapy","volume":"8","author":"Gerber","year":"2003","journal-title":"Drug Discov. Today"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.7314\/APJCP.2015.16.11.4571","article-title":"The inhibition effect of triptolide on human endometrial carcinoma cell line HEC-1B: A in vitro and in vivo studies","volume":"16","author":"Ni","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1038\/sj.onc.1204535","article-title":"Blockade of NF-\u03baB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis","volume":"20","author":"Huang","year":"2001","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.1158\/0008-5472.CAN-06-4277","article-title":"Inhibition of angiogenesis and invasion by 3,3\u2032-diindolylmethane is mediated by the nuclear factor-\u03baB downstream target genes MMP-9 and UPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer","volume":"67","author":"Kong","year":"2007","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"30353","DOI":"10.1074\/jbc.274.43.30353","article-title":"I\u03baB kinases phosphorylate Nf-\u03baB p65 subunit on serine 536 in the transactivation domain","volume":"274","author":"Sakurai","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18137","DOI":"10.1074\/jbc.M401397200","article-title":"Human T-cell lymphotropic virus type 1 tax induction of biologically active NF-\u03baB requires I\u03baB kinase-1-mediated phosphorylation of RelA\/p65","volume":"279","author":"Montano","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1074\/jbc.M208696200","article-title":"The NF-\u03baB activation in lymphotoxin \u03b2 receptor signaling depends on the phosphorylation of p65 at serine 536","volume":"278","author":"Jiang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"55633","DOI":"10.1074\/jbc.M409825200","article-title":"Constitutive and interleukin-1-inducible phosphorylation of p65 NF\u03baB at serine 536 is mediated by multiple protein kinases including I\u03baB kinase (IKK)-\u03b1, IKK\u03b2, IKK\u03b5, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription","volume":"279","author":"Buss","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7780","DOI":"10.1128\/MCB.23.21.7780-7793.2003","article-title":"Identification of NAP1, a regulatory subunit of I\u03baB kinase-related kinases that potentiates NF-\u03baB signaling","volume":"23","author":"Fujita","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"26115","DOI":"10.1074\/jbc.M313509200","article-title":"p53 Induces NF-\u03baB activation by an I\u03baB kinase-independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1","volume":"279","author":"Bohuslav","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1158\/0008-5472.CAN-04-3494","article-title":"Nuclear factor-\u03baB induced by doxorubicin is deficient in phosphorylation and acetylation and represses nuclear factor-\u03baB-dependent transcription in cancer cells","volume":"65","author":"Ho","year":"2005","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.immunol.14.1.649","article-title":"The NF-\u03baB and I\u03baB proteins: New discoveries and insights","volume":"14","author":"Baldwin","year":"1996","journal-title":"Annu. Rev. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/12\/2139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:53Z","timestamp":1760210933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/12\/2139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,19]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["ijms17122139"],"URL":"https:\/\/doi.org\/10.3390\/ijms17122139","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,19]]}}}