Parecoxib: an Enhancer of Radiation Therapy for Colorectal Cancer

  • Xiong, Wei ;
  • Li, Wen-Hui ;
  • Jiang, Yong-Xin ;
  • Liu, Shan ;
  • Ai, Yi-Qin ;
  • Liu, Rong ;
  • Chang, Li ;
  • Zhang, Ming ;
  • Wang, Xiao-Li ;
  • Bai, Han ;
  • Wang, Hong ;
  • Zheng, Rui ;
  • Tan, Jing
  • Published : 2015.02.25


Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.


Parecoxib;radiation;colorectal cancer;HCT116;HT29;microvessel density;microvessel intensity


  1. Armulik A, Abramsson A, Betsholtz C (2005). Endothelial/pericyte interactions. Circ Res, 97, 512-23.
  2. Birbrair A, Zhang T, Wang ZM, et al (2015). Pericytes at the intersection between tissue regeneration and pathology. Clin Sci (Lond), 128, 81-93.
  3. Chang L, Liu YY, Zhu B, et al (2009). High expression of the circadian gene mPer2 diminishes the radiosensitivity of NIH 3T3 cells. Braz J Med Biol Res, 42, 882-91.
  4. Chen FH, Chiang CS, Wang CC, et al (2009). Radiotherapy decreases vascular density and causes hypoxia with macrophage aggregation in TRAMP-C1 prostate tumors. Clin Cancer Res, 15, 1721-9.
  5. Dannenberg AJ, Subbaramaiah K (2003). Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell, 4, 431-6.
  6. Debucquoy A, Goethals L, Geboes K, et al (2006). Molecular responses of rectal cancer to preoperative chemoradiation. Radiother Oncol, 80, 172-7.
  7. de Lussanet QG, Backes WH, Griffioen AW, et al (2005). Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changesin rectal cancer. Int J Radiat Oncol Biol Phys, 63, 1309-15.
  8. Dou X, Wang RB, Yan HJ, et al (2013). Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases. Asian Pac J Cancer Prev, 14, 3881-5.
  9. Eberstal S, Badn W, Fritzell S, et al (2012). Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors. Cancer Immunol Immunother, 61, 1191-9.
  10. Harris RE, Casto BC, Harris ZM (2014). Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol, 5, 677-92.
  11. Khan Z, Khan N, Tiwari RP, et al (2011). Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets, 12, 1082-93.
  12. Kiguchi K, Ruffino L, Kawamoto T, et al (2007). Therapeutic effect of CS-706, a specific cyclooxygenase-2 inhibitor, on gallbladder carcinoma in BK5.ErbB-2 mice. Mol Cancer Ther, 6, 1709-17.
  13. Kim NK, Baik SH, Seong JS, et al (2006). Oncologic outcomes after neoadjuvant chemoradiation followed by curative resection with tumor-specific mesorectal excision for fixed locally advanced rectal cancer: Impact of postirradiated pathologic downstaging on local recurrence and survival. Ann Surg, 244, 1024-30.
  14. Kim YM, Pyo H (2013). Different cell cycle modulation by celecoxib at different concentrations. Cancer Biother Radiopharm, 28, 138-45.
  15. Kirane A, Toombs JE, Larsen JE, et al (2012a). Epithelialmesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib. Carcinogenesis, 33, 1639-46.
  16. Kirane A, Toombs JE, Ostapoff K, et al (2012b). Apricoxib, a novel inhibitor of COX-2, markedly improves standard therapy response in molecularly defined models of pancreatic cancer. Clin Cancer Res, 18, 5031-42.
  17. Koppe MJ, Oyen WJ, Bleichrodt RP, et al (2006). Combination therapy using the cyclooxygenase-2 inhibitor Parecoxib and radioimmunotherapy in nude mice with small peritoneal metastases of colonic origin. Cancer Immunol Immunother, 55, 47-55.
  18. Matsumoto S, Yasui H, Batra S, et al (2009). Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI. Proc Natl Acad Sci USA, 106, 17898-903.
  19. Pyo H, Choy H, Amorino GP, et al (2001). A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res, 7, 2998-3005.
  20. Raza A, Franklin MJ, Dudek AZ (2010). Pericytes and vessel maturation during tumor angiogenesis and metastasis. Am J Hematol, 85, 593-8.
  21. Sauer R, Becker H, Hohenberger W (2004). Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med, 351, 1731-40.
  22. Senzaki M, Ishida S, Yada A, et al (2008). CS-706, a novel cyclooxygenase-2 selective inhibitor, prolonged the survival of tumor-bearing mice when treated alone or in combination with anti-tumor chemotherapeutic agents. Int J Cancer, 122, 1384-90.
  23. Shin YK, Park JS, Kim HS, et al (2005). Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer Res, 65, 9501-9.
  24. Tang SC, Chen YC (2014). Novel therapeutic targets for pancreatic cancer. World J Gastroenterol, 20, 10825-44.
  25. Tsai JH, Makonnen S, Feldman M, et al (2005). Ionizing radiation inhibits tumor neovascularization by inducing ineffective angiogenesis. Cancer Biol Ther, 4, 1395-400.
  26. Yokouchi H, Kanazawa K, Ishida T, et al (2014). Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phase II trial and literature review. Mol Clin Oncol, 2, 744-50.
  27. Valentini V, Coco C, Picciocchi A, et al (2002). Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys, 53, 664-74.
  28. Watwe V, Javle M, Lawrence D, et al (2005). Cyclooxygenase-2 (COX-2) levels before and after chemotherapy: a study in rectal cancer. Am J Clin Oncol, 28, 560-4.

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Supported by : National Natural Science Foundation of China