title: Inflammatory processes of prostate tissue microenvironment drive rat prostate carcinogenesis: preventive effects of celecoxib.
abstract: 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-kappaB 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-kappaBp65, VEGF and TNF-alpha 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-kappaB p65 expression, induced apoptosis and tumor growth inhibition.
  
  
  CONCLUSIONS
  Carcinogen plus testosterone induced prostate carcinogenesis showing activation of macrophage, iNOS and NF-kappaBp65 could be prevented by celecoxib or related anti-inflammatory agents.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
authors.forename: Narayanan K
authors.initials: NK
authors.lastname: Narayanan
authors.forename: Dominick
authors.initials: D
authors.lastname: Nargi
authors.forename: Lori
authors.initials: L
authors.lastname: Horton
authors.forename: Bandaru S
authors.initials: BS
authors.lastname: Reddy
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
authors.forename: Bhagavathi A
authors.initials: BA
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis; D000068579:Celecoxib; D002455:Cell Division; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D052247:Nitric Oxide Synthase Type II; D000068579:Celecoxib