This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davis, T. W. Articles by Masferrer, J. L. Search for Related Content PubMed PubMed Citation Articles by Davis, T. W. Articles by Masferrer, J. L.

Synergy between Celecoxib and Radiotherapy Results from Inhibition of Cyclooxygenase-2-Derived Prostaglandin E₂, a Survival Factor for Tumor and Associated Vasculature

Oncology Discovery Research, Pfizer Corporation, St. Louis, Missouri

Previous work has demonstrated that selective cyclooxygenase-2 (COX-2) inhibitors can act synergistically with radiotherapy to improve tumor debulking and control in preclinical models. The underlying mechanism of this remarkable activity has not yet been determined. Here, we report that radiation can elevate intratumoral levels of COX-2 protein and its products, particularly prostaglandin E₂ (PGE₂). Furthermore, inhibition of COX-2 activity or neutralization of PGE₂ activity enhances radiotherapy even in tumors where COX-2 expression is restricted to the tumor neovasculature. Direct assessment of vascular function by direct contrast enhancement-magnetic resonance imaging showed that the combination of radiation and celecoxib lead to enhanced vascular permeability. These observations suggest that an important mechanism of celecoxib-induced radiosensitization involves inhibition of COX-2-derived PGE₂, thus removing a survival factor for the tumor and its vasculature.

This article has been cited by other articles:

				B. S. Min, Y. J. Choi, H. R. Pyo, H. Kim, J. Seong, H. C. Chung, S. Y. Rha, and N. K. Kim Cyclooxygenase-2 Expression in Pretreatment Biopsy as a Predictor of Tumor Responses After Preoperative Chemoradiation in Rectal Cancer Arch Surg, November 1, 2008; 143(11): 1091 - 1097. [Abstract] [Full Text] [PDF]

				A. B. Kunnumakkara, P. Diagaradjane, S. Guha, A. Deorukhkar, S. Shentu, B. B. Aggarwal, and S. Krishnan Curcumin Sensitizes Human Colorectal Cancer Xenografts in Nude Mice to {gamma}-Radiation by Targeting Nuclear Factor-{kappa}B-Regulated Gene Products Clin. Cancer Res., April 1, 2008; 14(7): 2128 - 2136. [Abstract] [Full Text] [PDF]

				P. de Heer, M. J.E.M. Gosens, E. C. de Bruin, N. G. Dekker-Ensink, H. Putter, C. A.M. Marijnen, A. J.C. van den Brule, J. H. J.M. van Krieken, H. J.T. Rutten, P. J.K. Kuppen, et al. Cyclooxygenase 2 Expression in Rectal Cancer Is of Prognostic Significance in Patients Receiving Preoperative Radiotherapy Clin. Cancer Res., May 15, 2007; 13(10): 2955 - 2960. [Abstract] [Full Text] [PDF]

				D Wang and R N DuBois PROSTAGLANDINS AND CANCER Gut, January 1, 2006; 55(1): 115 - 122. [Full Text] [PDF]

				S. T. Palayoor, M. J. Arayankalayil, A. Shoaibi, and C. N. Coleman Radiation Sensitivity of Human Carcinoma Cells Transfected with Small Interfering RNA Targeted against Cyclooxygenase-2 Clin. Cancer Res., October 1, 2005; 11(19): 6980 - 6986. [Abstract] [Full Text] [PDF]

				X. Zhang, Z. Chen, M. S. Choe, Y. Lin, S.-Y. Sun, H. S. Wieand, H. J. C. Shin, A. Chen, F. R. Khuri, and D. M. Shin Tumor Growth Inhibition by Simultaneously Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Xenograft Model Clin. Cancer Res., September 1, 2005; 11(17): 6261 - 6269. [Abstract] [Full Text] [PDF]

				S. Sharma, S.-C. Yang, L. Zhu, K. Reckamp, B. Gardner, F. Baratelli, M. Huang, R. K. Batra, and S. M. Dubinett Tumor Cyclooxygenase-2/Prostaglandin E2-Dependent Promotion of FOXP3 Expression and CD4+CD25+ T Regulatory Cell Activities in Lung Cancer Cancer Res., June 15, 2005; 65(12): 5211 - 5220. [Abstract] [Full Text] [PDF]

				M. Ladetto, S. Vallet, A. Trojan, M. Dell'Aquila, L. Monitillo, R. Rosato, L. Santo, D. Drandi, A. Bertola, P. Falco, et al. Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome Blood, June 15, 2005; 105(12): 4784 - 4791. [Abstract] [Full Text] [PDF]

				H.-P. Lin, S. K. Kulp, P.-H. Tseng, Y.-T. Yang, C.-C. Yang, C.-S. Chen, and C.-S. Chen Growth inhibitory effects of celecoxib in human umbilical vein endothelial cells are mediated through G1 arrest via multiple signaling mechanisms Mol. Cancer Ther., December 1, 2004; 3(12): 1671 - 1680. [Abstract] [Full Text] [PDF]