Parecoxib: an Enhancer of Radiation Therapy for Colorectal Cancer

Abstract

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.

The Cyclooxigenase-2 Inhibitor Parecoxib Prevents Epidermal Dysplasia in HPV16-Transgenic Mice: Efficacy and Safety Observations

“…Parecoxib, a water-soluble prodrug which is biotransformed in the liver by enzymatic hydrolysis and converted into its active metabolite, valdecoxib, is a selective COX-2 inhibitor used to minimize postoperative pain in noncardiac surgeries. It is also the only selective NSAID marketed that allows parenteral administration [17,18].…”

“…In the present work, we chose a different COX-2 inhibitor, parecoxib, to achieve chemopreventive and toxicological studies in vivo using the same animal model. Parecoxib is a water-soluble prodrug of valdecoxib [15,16] and is the only selective COX-2 inhibitor that can be administered parenterally, which may contribute to a different toxicological profile compared to other COX-2 inhibitors such as celecoxib [17,18].…”

Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review)

“…Parecoxib is another important selective COX-2 inhibitor, with high postoperative pain control and less side effects ( 106 ). Treatment with parecoxib has exhibited a promising anticancer role in different types of human cancer ( 106 , 107 ).…”

“…Parecoxib is another important selective COX-2 inhibitor, with high postoperative pain control and less side effects ( 106 ). Treatment with parecoxib has exhibited a promising anticancer role in different types of human cancer ( 106 , 107 ). The latest research suggests that parecoxib inhibits the proliferation, migration and invasion of glioblastoma cells by upregulating miR-29c expression ( 108 ).…”

Parecoxib inhibits glioblastoma cell proliferation, migration and invasion by up-regulating miRNA-29c

“…Accumulating data indicated that COX-2 inhibitors, the non-steroidal anti-inflammatory drugs, are promising chemoprevention and chemotherapeutic agents that may protect against breast, brain, lung, esophageal, colon, and oral tumors ( Dang et al, 2002 ; Menter, 2002 ). Of the COX-2 inhibitors, parecoxib is one of the most well-known COX-2 selective inhibitors, which had been developed as a highly efficient postoperative analgesia drug with low adverse reaction, and parecoxib treatment was shown to exert a potent anticancer role in multiple human cancers, including colorectal cancer ( Zagani et al, 2009 ; Xiong et al, 2015 ), esophageal adenocarcinoma ( Santander et al, 2012 ). It is worth noting that parecoxib treatment was capable of enhancing immunotherapy of brain tumors.…”