Multifunctional role of VIP in prostate cancer progression in a xenograft model: Suppression by curcumin and COX-2 inhibitor NS-398

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2009-12, Vol.30 (12), p.2357-2364
• Main Authors: Fernández-Martínez, Ana B., Bajo, Ana M., Valdehita, Ana, Isabel Arenas, M., Sánchez-Chapado, Manuel, Carmena, María J., Prieto, Juan C.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; COX-2; Curcumin; Curcumin - pharmacology; Curcumin - therapeutic use; Cyclooxygenase 2; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Male; Male genital diseases; Matrix Metalloproteinase 2 - metabolism; Matrix metalloproteinases; Medical sciences; Mice; Mice, Nude; Nephrology. Urinary tract diseases; Nitrobenzenes - pharmacology; Nitrobenzenes - therapeutic use; Polymerase Chain Reaction; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vasoactive Intestinal Peptide - genetics; Vasoactive Intestinal Peptide - pharmacology; Vasoactive Intestinal Peptide - physiology; Vertebrates: endocrinology; VIP; Xenograft Model Antitumor Assays
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2009.09.018

We used an in vivo model of human experimental prostate cancer in order to shed a new light on the effects of vasoactive intestinal peptide (VIP) on tumor growth as well as its pro-metastatic potential in this disease. We used nude mice subcutaneously injected with prostate cancer androgen-independent PC3 cells for 30 days. The regulatory role of VIP on cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expression as well as on matrix metalloproteinase-2 and 9 (MMP-2 and 9) activities was examined. A selective COX-2 inhibitor, NS-398, and curcumin were used to block VIP effects. Xenografts of VIP-treated PC3 prostate cancer cells in nude mice gave tumors that grew significantly faster than those in the untreated group. It is conceivably a result of both the trophic effect of VIP on prostate cancer cells and the proangiogenic action of the neuropeptide in the growing tumor. We show the overexpression at mRNA and/or protein levels of VIP, its main receptor VPAC 1, the major angiogenic factor VEGF, and the pro-inflammatory enzyme COX-2 as well as the increased activity of MMP-2 and 9 in tumors derived from VIP-treated PC3 cells as compared with control group. The overexpression of the above biomarkers was suppressed in tumors derived from VIP-treated PC3 cells that had been previously incubated with curcumin or NS-398. Thus, the potential therapeutic role of curcumin and selective COX-2 inhibitors in combination with available VIP antagonists should be considered in prostate cancer therapy as supported by their inhibitory activities on tumor cell growth.