The role of cyclooxygenase-2 in prostate cancer.
Cyclooxygenase-2 (COX-2) is the inducible isozyme of COX, a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. COX-2 is highly expressed in a number of human cancers and cancer cell lines, including prostate cancer. We studied the immunohistochemical expression of COX-2 in the human prostate gland. The enzyme is strongly expressed in smooth muscle cells of both the normal and cancerous prostate. Its expression in noncancerous epithelial cells is limited to the basal cell layer. In prostatic inflammation, luminal epithelial cells surrounded by lymphocytes are induced to express the enzyme. COX-2 is expressed in the epithelial cells of high-grade prostatic intraepithelial neoplasia and cancer. We have demonstrated that treatment of human prostate-cancer cell lines with a selective COX-2 inhibitor induces apoptosis both in vitro and in vivo. The in vivo results also indicate that the COX-2 inhibitor decreases tumor microvessel density and angiogenesis. COX-2 inhibitors can prevent the hypoxic upregulation of a potent angiogenic factor, vascular endothelial growth factor. These results indicate that COX-2 inhibitors may, therefore, serve as effective chemopreventive and therapeutic agents in cancer of the prostate.
Kirschenbaum
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A
Department ofUrology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Liu
X
X
Yao
S
S
Levine
A C
AC
D000818:Animals; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D014407:Tumor Cells, Cultured / Q000201:enzymology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases