We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like Nexrutine, demonstrating a prospective for development of Nexrutine for prostate cancer management.
We have explored the role of COX-2 in prostate cancer in terms of attenuation of apoptosis and sensitivity to pharmacological agents, including COX-2 inhibitors.
To evaluate the potential role of COX-2 in prostate cancer, LNCaP cells were treated with NS398, a selective COX-2 inhibitor, and the effects on cell viability and apoptosis were determined.
To elucidate the effects of COX-2 on p53 in response to hypoxia, we transfected the COX-2 gene into the p53-positive, COX-2-negative MDA-PCa-2b human prostate cancer cell line.
These data demonstrate that COX-2 contributes to prostate cancer progression and suggest that it mediates this effect, in part, through increased VEGF.
Therefore, this feedback loop may be relevant in prostate cancer for the maintenance of PGE<sub>2</sub> -dependent cancer cell growth through amplifying the activity of the COX-2 pathway.
The importance of HIF-1alpha in tumor progression makes it a logical target for chemoprevention strategies in patients at higher genetic risk of breast and prostate cancer with Cox 2 inhibitors or 2-methoxyestradiol, as well as a target for new approaches to inhibiting angiogenesis.
The expression of Ki-67, PSCA, and Cox-2 biomarkers along with other clinicopathologic factors were prognostic factors for BCR in patients with clinically localized prostate cancer following radical prostatectomy.
Since increased Cox-2 expression is associated with an increased incidence of prostate cancer, and decrease in its expression by SPBE would provide a basis for further investigation of its use against BPH and in prostatic cancer chemoprevention.
Overall, these results provide strong evidence for the role of COX-2 and Glut-1 proteins for the progression of prostate cancer and highlighting the potential of celecoxib and genistein as a useful and combinatorial pharmacological agent for chemotherapeutic purposes in prostate cancer.
Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion.
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.
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.
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.
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.
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.