| Title | Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. | | Author(s) | Liu XH, Kirschenbaum A, Yao S, Lee R, Holland JF, Levine AC | | Institution | Departments of Urology and Medicine, Divisions of Endocrinology and Neoplastic Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA. | | Source | J Urol 2000 Sep; 164(3 Pt 1):820-5. | | MeSH | Animals
Apoptosis
Comparative Study
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Disease Models, Animal
Endothelial Growth Factors
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
In Situ Nick-End Labeling
Injections, Intraperitoneal
Isoenzymes
Lymphokines
Male
Membrane Proteins
Mice
Mice, Nude
Microcirculation
Neoplasm Transplantation
Neovascularization, Pathologic
Nitrobenzenes
Peroxidases
Proliferating Cell Nuclear Antigen
Prostaglandin-Endoperoxide Synthases
Prostatic Neoplasms
Protein Isoforms
Random Allocation
Research Support, Non-U.S. Gov't
Sulfonamides
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Vehicles
von Willebrand Factor
| | Abstract | PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme which catalyzes the formation of prostaglandins from arachidonic acid, is expressed in prostate cancer specimens and cell lines. To evaluate the in vivo efficacy of a COX-2 inhibitor in prostate cancer, NS398 was administered to mice inoculated with the PC-3 human prostate cancer cell line.
MATERIALS AND METHODS: A total of 28 male nude mice were inoculated subcutaneously with 1 million PC-3 cells. Tumors were palpable in all 28 animals 1 week after inoculation and mice were randomized to receive either vehicle (control) or NS398, 3 mg./kg. body weight, intraperitoneally three times weekly for 9 weeks. Tumors were measured at weekly intervals. After a 10-week experimental period, mice were euthanized and tumors were immuno- histochemically assayed for proliferation (PCNA), apoptosis (TUNEL) and microvessel density (MVD) (Factor-VIII-related antigen). Tumor VEGF content was assayed by Western blotting.
RESULTS: NS398 induced a sustained inhibition of PC-3 tumor cell growth and a regression of existing tumors. Average tumor surface area from control mice was 285 mm.2 as compared with 22 mm.2 from treated mice (93% inhibition, p <0.001). Immunohistochemical analysis revealed that NS398 had no effect on proliferation (PCNA), but induced apoptosis (TUNEL) and decreased MVD (angiogenesis). VEGF expression was also significantly down regulated in the NS398-treated tumors.
CONCLUSIONS: These results demonstrate that a selective COX-2 inhibitor suppresses PC-3 cell tumor growth in vivo. Tumor growth suppression is achieved by a combination of direct induction of tumor cell apoptosis and down regulation of tumor VEGF with decreased angiogenesis | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 10953162 |
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