Non-small-cell lung cancer (NSCLC), especially adenocarcinomas, overexpress COX-2, which contributes to the progression of malignancy by several mechanisms.
Aberrant CpG island methylation, and subsequent silencing of the COX-2 promoter, has been observed in human cancer cell lines and in some human tumors of the gastrointestinal tract.
COX-2 messenger RNA (mRNA) was detected in 3 of 4 patients with Dukes' stage A, 13 of 14 patients with Dukes' stage B, and 10 of 11 patients with Dukes' stage C or D. COX-2 mRNA was detected in 5 of 7 patients with proximal cancer and in 21 of 22 patients with distal cancer.
To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to overexpression of COX-2, we studied expression of HuR in 208 primary breast carcinomas by immunohistochemistry.
Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells.
COX-2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor-associated microvessels).
Whereas COX-2 and PGE(2) are associated with cancer cell survival and tumor angiogenesis, arachidonic acid itself is a strong apoptotic signal that may facilitate cancer cell death.
Inhibition of COX-2 by nonsteroidal antiinflammatory drugs reduces the risk of cancer development in humans and suppresses tumor growth in animal models.
Our data demonstrated that IL-1alpha and COX-2 mRNA were frequently co-expressed in human gastric cancer tissues, and suggested that the IL-1alpha-COX-2 pathway might be involved in tumor progression by regulating cancer cell proliferation.
In addition, COX-2 mRNA, matrix metalloproteinase (MMP)-9 mRNA, and tissue inhibitor of MMP (TIMP)-1 mRNA of cancer tissue were measured by means of real-time RT-PCR.
Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer.
Expression of COX-2 and p53 proteins was examined by immunohistochemistry in paraffin-embedded cancer tissue blocks, and the relationship between COX-2 and/or p53 expression with clinicopathologic parameters was analyzed.
Increased cytoplasmic HuR expression occurs in several cancer types, including colorectal cancer where it may contribute to the increased cyclooxygenase-2 (COX- 2) expression observed during tumorigenesis.
For the two latter, NSAID use was only associated with a lower cancer risk among homozygous wild type allele carriers. p for interaction was 3 x 10(-6) for COX-2A-1195G and 9 x 10(-5) for PPARgamma2 Pro(12)Ala.
To investigate whether the COX-2 -765 G>C promoter polymorphism (known to lead to a reduction of COX-2 promoter activity in the colon) may explain this difference in expression, we carried out single-nucleotide polymorphism (SNP) analysis of 241 gastric cancers, including early-onset gastric cancer, conventional gastric cancers and gastric stump cancers, as well as in 100 control patients, using real-time PCR and sequence analysis, and correlated these findings with COX-2 expression using immunohistochemistry.
Moreover, curcumin inhibits microvascular endothelial cell angiogenesis through inhibition of COX-2 expression and PGE(2) production, suggesting that this natural product possesses antiangiogenic properties, which warrants further investigation as adjuvant treatment of IBD and cancer.