Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis
Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis
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DOI：
10.1111/cas.12292
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发表时间：
2013-12-01
期刊：
影响因子：
5.7
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Suzuki, Shugo;Shiraga, Kazuhide;Takahashi, Satoru
最近的证据表明，氧化应激有助于前列腺癌的发病机制。本研究采用前列腺腺癌转基因大鼠（TRAP）模型，观察了NADPH氧化酶抑制剂夹竹桃素对前列腺癌发生的影响。夹竹桃麻素治疗无毒性作用。在腹侧和侧前列腺癌的百分比和数量显着减少夹竹桃麻素治疗，剂量依赖性。通过8-OHdG和二氢乙锭染色的免疫组化证实了夹竹桃素对活性氧的减少。夹竹桃麻素处理组Ki 67阳性率显著降低，clusterin表达下调以及MEK-ERK 1/2通路失活是夹竹桃麻素处理组的特征。在人前列腺癌细胞系LNCaP中，夹竹桃麻素还通过下调clusterin和cyclin D1诱导G 0/G1期阻滞来抑制活性氧的产生并阻断细胞生长。这些数据表明，夹竹桃麻素具有化学预防前列腺癌的潜力。
Recent evidence suggests that oxidative stress contributes to the pathogenesis of prostate cancer. The present study focused on the effect of apocynin, an inhibitor of NADPH oxidase, on prostate carcinogenesis using the transgenic rat for adenocarcinoma of prostate (TRAP) model. There were no toxic effects with apocynin treatment. The percentages and numbers of carcinomas in both the ventral and lateral prostate were significantly reduced by apocynin treatment, with dose dependence. Reduction of reactive oxygen species by apocynin was confirmed by immunohistochemistry of 8-OHdG and dihydroethidium staining. Positivity of Ki67 was significantly reduced by apocynin treatment, and downregulation of clusterin expression, as well as inactivation of the MEK-ERK1/2 pathway, was a feature of the apocynin treated groups. In human prostate cancer cell line LNCaP, apocynin also inhibited reactive oxygen species production and blocked cell growth by inducing G0/G1 arrest with downregulation of clusterin and cyclin D1. These data suggest that apocynin possesses chemopreventive potential against prostate cancer.