Different types of cox enzymes with their functions. It's role in cancer and how it can effectively help with other drugs therapy in cancer treatment.

1. COX-2 role in cancer
Mr. Abhijeet G. Parkhe

3. Treatment with CAB (Combined androgen blockade therapy) and HF
(Hydroxyflutamide) therapy results in the increased COX-2 expression in
prostate cancer patients:
•Protein expression in clinical specimens from prostate cancer patients before and
after combined androgen blockade (CAB) therapy.
•Three pairs of prostate tumor specimens obtained from patients before and after
CAB therapy were subjected to the COX-2 immunostaining.
•As shown in Figure 5, very weak COX-2 expression was detected mainly in the
cytoplasm of luminal epithelial cells in all 3 specimens before androgen ablation
therapy.
•In contrast, an enhanced and strong COX-2 expression was detected in both the
cytoplasm and nuclei of epithelial cells in all specimens from the same patients after
CAB therapy.

5. In conclusion:
• Androgen and its receptor play an inhibitory role in COX-2 expression in prostate
cancer cells.
•COX-2 overexpression in prostate cancer is due to androgen ablation, and might result
in the failure of CAB therapy.
•Findings suggest that cotreatment with COX-2 inhibitor(s) could diminish prostate
cancer progression induced by androgen ablation therapy.

6. COX-2-dependent stabilization of survivin (Member of apoptosis family – act by
negetive regulation of apoptosis) In non-small cell lung cancer:
IMP points:
•The mechanism(s) by which COX-2 exerts its cytoprotective effects are not
completely understood but may be due to an imbalance of pro- and anti-apoptotic
gene expression.
•Nonsteroidal anti-inflammatory drugs (NSAIDS) as well as specific COX-2 inhibitors
increase the susceptibility of cancer cells to apoptosis
•A COX-2 metabolite abundantly present in the lung cancer microenvironment.

8. Molecular Pathology of Cyclooxygenase-2 in Cancer-induced Angiogenesis:
•A COX-2 metabolite abundantly present in the lung cancer microenvironment
•COX-2 is strongly expressed and produces pro-inflammatory prostaglandins such as PGE2.
•PGE2 can induce VEGF.
•COX-2 and VEGF are both expressed in rat sponge-implant-angiogenesis.
•COX-2 is located in the endothelial cells of the new vessels that are formed in the sponge-
granuloma tissue.
•The experimental angiogenesis can be blocked by either a non-selective NSAID,
indomethacin, or by selective COX-2 inhibitors, NS-398 or JTE-522, as well as by VEGF
anti-sense oligonucleotides.
•COX-2 is important because it induces metalloproteinase and strongly induces VEGF, the
common angiogenic factor, which thereupon directs tumor-induced angiogenesis.
•Enhanced COX-2 expression has been demonstrated in numerous types of cancer cells and
tissues, such as colorectal cancer.
•Prostatic tissue cancer cells showed significantly elevated, mainly intracytoplasmic,
expression of COX-2.

9. •In a study of 100 patients with colon cancer, those with COX-2-expressing tumors had
significantly shorter survival time than those with COX-2-negative tumors.
• In vitro, hypoxia induces COX-2, increases PGE2 synthesis, elevates the VEGF level, and
induces angiogenesis. The selective COX-2 inhibitor NS-398 can block this process.
•Hypoxia induced by cobalt chloride markedly increased COX-2 and upregulated VEGF
via PGE2 in the cultured, highly invasive PC-3ML prostate-carcinoma cell line.
•Human cytomegalovirus (CMV) inactivates wild type p53 of diverse cell types resulting in
loss of inhibition of COX-2 expression and enhanced angiogenesis.

10. References:
1. Review: Molecular Pathology of Cyclooxygenase-2 in Cancer-induced
Angiogenesis, Egil Fosslien et al. 2001.
2. COX-2-dependent stabilization of survivin in non-small cell lung cancer,
Kostyantyn Krysan et al 2003.
3. A new prostate cancer therapeutic approach: Combination of androgen ablation with
COX-2 inhibitor, Yi Cai et al. 2008.