恩扎鲁胺
前列腺癌
多西紫杉醇
医学
雄激素受体
肿瘤科
癌症
内科学
癌症研究
蛋白激酶B
信号转导
生物
生物化学
作者
Masaki Shiota,Masahiro Ushijima,Kenjiro Imada,Eiji Kashiwagi,Ario Takeuchi,Junichi Inokuchi,Katsunori Tatsugami,Shunichi Kajioka,Masatoshi Eto
出处
期刊:The Prostate
[Wiley]
日期:2019-05-11
卷期号:79 (10): 1147-1155
被引量:5
摘要
Abstract Background Cigarette smoking is associated with worse outcomes in prostate cancer, whose growth is dependent on androgen receptor (AR) signaling. We aimed to elucidate the biological effect of cigarette smoking on AR signaling and its clinical influence on oncological outcome. Methods Gene expression levels after exposure to tobacco smoke condensate (TSC) were evaluated by quantitative real‐time polymerase chain reaction and Western blot analysis in prostate cancer cells. Cellular sensitivities to enzalutamide and docetaxel after TSC exposure were evaluated using a prostate cancer cell proliferation assay. Prognosis was compared between current smokers and nonsmokers when treated with AR‐axis‐targeting (ARAT) agent enzalutamide and docetaxel. Results Expression of AR variants as well as prostate‐specific antigen was augmented after TSC exposure, which occurred after Akt phosphorylation. These inductions were suppressed by Akt inhibitor LY294002 as well as antioxidant N‐acetylcysteine. Consistently, TSC exposure augmented cellular resistance to enzalutamide. In clinical data, cigarette smoking was associated with worse progression‐free survival and cancer‐specific survival when patients with prostate cancer were treated with ARAT agents but not docetaxel. Conclusions It was suggested that cigarette smoking leads to detrimental oncological outcome when prostate cancer patients are treated with ARAT agents through induction of aberrant AR signaling. Accordingly, we recommend that patients with advanced prostate cancer should refrain from cigarette smoking.
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