Premium
Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: Preventive effects of celecoxib
Author(s) -
Narayanan Narayanan K.,
Nargi Dominick,
Horton Lori,
Reddy Bandaru S.,
Bosland Maarten C.,
Narayanan Bhagavathi A.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20862
Subject(s) - prostate , prostate cancer , inflammation , medicine , carcinogenesis , endocrinology , monocyte , cancer research , cancer
BACKGROUND Prostate tissue microenvironment is susceptible to several risk factors including carcinogens, dietary factors, hormones, cytokines and growth factors that could induce chronic inflammation. Because of the difference in the serum levels and the intrinsic ability of monocytes/macrophages to cause harm, the transcriptional responses triggered by inflammatory stimuli must be controlled. Unfortunately, an in‐depth association between prostate cancer and potential mediators of inflammation has not been completely investigated. METHODS To determine whether activated macrophage (infiltrating monocytes), iNOS and NF‐κB are primary mediators of inflammation, besides COX‐2, in prostate carcinogenesis, we examined tissue sections of rat prostate tumor induced by N ‐methyl‐ N ‐nitrosourea (MNU) plus testosterone in a follow‐up study. We performed H&E and immunohsitochemical staining of the prostate tissue to detect specific markers of inflammation. RESULTS We report an increase in infiltrating monocyte, iNOS, NF‐κBp65, VEGF and TNF‐α at the early and advanced stages of tumor growth in MNU plus testosterone treated rats. Monocyte infiltration was often found in the stromal and perivascular regions of the DL prostate. We conclude for the first time that prostate cancer induced by MNU plus testosterone partly involves mediators of inflammation which could trigger the process of carcinogenesis and cause loss of apoptosis. Selective COX‐2 inhibitor celecoxib at a dose of 500 mg/kg/bw administered for 52 weeks reduced infiltrating monocytes, inhibited iNOS, NF‐κB p65 expression, induced apoptosis and tumor growth inhibition. CONCLUSION Carcinogen plus testosterone induced prostate carcinogenesis showing activation of macrophage, iNOS and NF‐κBp65 could be prevented by celecoxib or related anti‐inflammatory agents. Prostate 69: 133–141, 2009. © 2008 Wiley–Liss, Inc.