{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:57:48Z","timestamp":1780055868985,"version":"3.54.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,8,1]],"date-time":"2004-08-01T00:00:00Z","timestamp":1091318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The cyclooxygenase 2 (COX-2) inhibitor celecoxib (also called celebrex), approved for the treatment of colon carcinogenesis, rheumatoid arthritis, and other inflammatory diseases, has been shown to induce apoptosis and inhibit angiogenesis. Because NF-\u03baB plays a major role in regulation of apoptosis, angiogenesis, carcinogenesis, and inflammation, we postulated that celecoxib modulates NF-\u03baB. In the present study, we investigated the effect of this drug on the activation of NF-\u03baB by a wide variety of agents. We found that celecoxib suppressed NF-\u03baB activation induced by various carcinogens, including TNF, phorbol ester, okadaic acid, LPS, and IL-1\u03b2. Celecoxib inhibited TNF-induced I\u03baB\u03b1 kinase activation, leading to suppression of I\u03baB\u03b1 phosphorylation and degradation. Celecoxib suppressed both inducible and constitutive NF-\u03baB without cell type specificity. Celecoxib also suppressed p65 phosphorylation and nuclear translocation. Akt activation, which is required for TNF-induced NF-\u03baB activation, was also suppressed by this drug. Celecoxib also inhibited the TNF-induced interaction of Akt with I\u03baB\u03b1 kinase (IKK). Celecoxib abrogated the NF-\u03baB-dependent reporter gene expression activated by TNF, TNF receptor, TNF receptor-associated death domain, TNF receptor-associated factor 2, NF-\u03baB-inducing kinase, and IKK, but not that activated by p65. The COX-2 promoter, which is regulated by NF-\u03baB, was also inhibited by celecoxib, and this inhibition correlated with suppression of TNF-induced COX-2 expression. Besides NF-\u03baB, celecoxib also suppressed TNF-induced JNK, p38 MAPK, and ERK activation. Thus, overall, our results indicate that celecoxib inhibits NF-\u03baB activation through inhibition of IKK and Akt activation, leading to down-regulation of synthesis of COX-2 and other genes needed for inflammation, proliferation, and carcinogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.173.3.2011","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T23:38:25Z","timestamp":1398209905000},"page":"2011-2022","source":"Crossref","is-referenced-by-count":163,"title":["Cyclooxygenase (COX)-2 Inhibitor Celecoxib Abrogates TNF-Induced NF-\u03baB Activation through Inhibition of Activation of I\u03baB\u03b1 Kinase and Akt in Human Non-Small Cell Lung Carcinoma: Correlation with Suppression of COX-2 Synthesis"],"prefix":"10.1093","volume":"173","author":[{"given":"Shishir","family":"Shishodia","sequence":"first","affiliation":[{"name":"Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimpy","family":"Koul","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat B","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,8,1]]},"reference":[{"key":"2026020212053920800_R1","first-page":"331","volume-title":"Clin. Rheumatol.","year":"2000"},{"key":"2026020212053920800_R2","first-page":"1946","volume-title":"N. Engl. J. 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