脂连素抑制人前列腺癌细胞氧化应急 Adiponectin inhibits oxidative stress in prostate carcinoma cells.pdfVIP

Prostate Cancer and Prostatic Diseases (2012), 1–8 2012 Macmillan Publishers Limited All rights reserved 1365-7852/12 /pcan ORIGINAL ARTICLE Adiponectin inhibits oxidative stress in human prostate carcinoma cells J-P Lu1,2, ZF Hou1,2, WC Duivenvoorden1,2, K Whelan1,2, A Honig1,2 and JH Pinthus1,2 1Division of Urology, Department of Surgery, McMaster University, Hamilton, Ontario, Canada and 2Department of Surgical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada BACKGROUND: Emerging data suggest that obesity increases the risk of aggressive prostate cancer (PC), but the mechanisms underlying this relationship remain to be fully elucidated. Oxidative stress (OS) is a key process in the development and progression of PC. Adiponectin, an adipocyte-specific hormone, circulates at relatively high levels in healthy humans, but at reduced levels in obese subjects. Moreover, case–control studies also document lower levels of serum adiponectin in PC patients compared with healthy individuals. METHODS: Human 22Rv1 and DU-145 PC cell lines were examined for the generation of OS and detoxification of reactive oxygen species after treatment with adiponectin. Normality was confirmed using the Shapiro–Wilk test and results were analyzed using a one-way analysis of variance. RESULTS: We demonstrate that adiponectin increased cellular anti-oxidative defense mechanisms and inhibited OS in a significant and dose-dependent manner. We show that adiponectin treatment decreased the generation of superoxide anion in both cell lines, whereas the transcript levels of NADPH oxidase (NOX)2 and NOX4 increased. We also found indications of an o