Non-small-cell lung cancer (NSCLC), especially adenocarcinomas, overexpress COX-2, which contributes to the progression of malignancy by several mechanisms.
Non-small cell lung cancercyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production.
As reported previously for COX-2, levels of mPGES mRNA and protein were increased in NSCLC cell lines containing mutant Ras as compared with a nontumorigenic bronchial epithelial cell line.
Because preclinical data indicated that tumor COX-2 expression caused resistance to EGFR TKI, a phase I trial to establish the optimal biological dose (OBD), defined as the maximal decrease in urinary prostaglandin E-M (PGE-M), and toxicity profile of the combination of celecoxib and erlotinib in advanced non-small cell lung cancer was done.
Because tumor COX-2 expression appears to have a multifaceted role in conferring the malignant phenotype, COX-2 may be an important target for gene or pharmacologic therapy in NSCLC.
Celecoxib (Celebrex) is a cyclooxygenase-2 (COX-2) selective inhibitor and gefitinib (Iressa(R), ZD1839) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for human non-small cell lung cancer (NSCLC).
Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression.
Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non-small cell lung cancer (NSCLC).
Consistent with the proposed growth promoting role of PGE2, we found that NSCLC cell lines frequently co-expressed the genes encoding cyclooxygenase-2 and the prostaglandin E2 (PGE2) receptors EP1, 2 and 4 concomitant with the synthesis of PGE2.
Correction: Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression.
Genes PTGS2 (COX2), CALCA, MTHFR, ESR1, MGMT, MYOD1, and APC showed statistically significant differences in the level of CpG island methylation between small cell lung cancer (SCLC) and non-small cell lung cancer cell lines (NSCLC).
Here we investigated the effect of eicosapentaenoic acid (EPA) on the proliferation of human non-small cell lung cancer A549 (COX-2 over-expressing) and H1299 (COX-2 null) cells as well as their xenograft models.
However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy.