This study investigated the addition of celecoxib, a selective COX-2 inhibitor, to the irinotecan, 5-fluorouracil, and leucovorin (IFL) regimen for patients with previously untreated metastatic CRC.
In the prostaglandin-dependent pathways, inhibition of cyclooxygenase (COX), particularly COX-2, is the primary mechanism known to be involved in aspirin-induced CRC suppression.
The aim of this study is to investigate the relationship between the status of COX-2 expression in the primary CRC and the characteristics of recurrence after curative resection of stage I to III CRC.
IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations).
Overall, it was concluded that NSAIDs, particularly cyclooxygenase-2 (COX-2) inhibitors, might have a protective effect on CRC development and slow down progression of tumor in a DMH-induced experimental cancer model.
On the other hand, NPX and other NSAIDs are extensively studied in terms of colorectal cancer (CRC) prevention and inhibition, since it has been evidenced that COX-2 corresponds with the risk of the tumor occurrence and growth.
In conclusion, our study provided the evidence towards better antiproliferative effect of AR13 and AR15 in DMH-induced CRC through the blockade of COX-2/JAK-2/STAT-3 signal transduction pathway and could be demonstrated as useful anti-CRC candidate molecules for future anticancer therapy.
A mechanistic analysis revealed that YAP1 promoted CRC-derived MDSC induction by suppressing PTEN expression to up-regulate COX-2, P-AKT and P-p65 in CRC-derived cells, leading to secretion of the cytokine granulocyte-macrophage colony-stimulating factor.
Our study suggests that meat intake may activate TLRs at the epithelial surface, leading to CRC via inflammation by nuclear transcription factor-κB-initiated transcription of inflammatory genes, whereas intake of fiber may protect against CRC via TLR4-mediated secretion of interleukin-10 and cyclooxygenase-2.
Colorectal cancers exhibit a high level of cyclooxygenase-2 (COX-2) expression with strong preclinical rationale for improved clinical outcomes with COX-2 inhibition.
Prostaglandin E2 (PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer.
In the present review, we provide published evidence to demonstrate that (1) COX-2 signaling plays a major role in the progression of colorectal cancer, (2) activation of COX-2 in the stromal compartment also contributes to colorectal carcinogenesis, and (3) inhibition of COX-2 signaling by COX-2 inhibitors might be an effective method to control colorectal cancer.
Here we showed that the addition of the COX-2 inhibitor celecoxib improved the antitumor efficacy in colorectal cancer (CRC) of the monoclonal anti-EGFR antibody cetuximab.