Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications.
All-NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61-0.98, especially in men using NSAIDs that preferentially inhibit COX-2 activity (OR 0.48, 95% CI 0.28-0.79).
Although HER2 does not drive COX2 expression in prostate cancer, this study identified high levels of COX2 expressed in locally advanced prostate cancer, suggesting COX2 could be a potential therapeutic target.
Although it is low in stromal and tumor cells, COX-2 expression is induced by TNF-alpha in these cells, and this responsiveness may play an important role in prostate cancer progression.
Among the six polymorphic sites examined, only the Cox-2 promoter G-765C (rs14133) genotypes were distributed differently between the prostate cancer and control groups.
Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers.
In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model.
In conclusion, NFKB1 -94 ins/del and COX-2 (-1195G>A) polymorphisms may be, respectively, associated with decreased and increased prostate cancer risk in the Chinese population.
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways.
Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.<b>Conclusions:</b> Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment.<i></i>.