Tatsumi Kenichiro, Hirotsu Akiko, Daijo Hiroki, Matsuyama Tomonori, Terada Naoki, Tanaka Tomoharu
Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Anesthesia, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-0861, Japan.
Eur J Pharmacol. 2017 Aug 15;809:242-252. doi: 10.1016/j.ejphar.2017.05.046. Epub 2017 May 25.
Androgen receptor is a nuclear receptor and transcription factor activated by androgenic hormones. Androgen receptor activity plays a pivotal role in the development and progression of prostate cancer. Although accumulating evidence suggests that general anesthetics, including opioids, affect cancer cell growth and impact patient prognosis, the effect of those drugs on androgen receptor in prostate cancer is not clear. The purpose of this study was to investigate the effect of the general anesthetic propofol on androgen receptor activity in prostate cancer cells. An androgen-dependent human prostate cancer cell line (LNCaP) was stimulated with dihydrotestosterone (DHT) and exposed to propofol. The induction of androgen receptor target genes was investigated using real-time reverse transcription polymerase chain reaction, and androgen receptor protein levels and localization patterns were analyzed using immunoblotting and immunofluorescence assays. The effect of propofol on the proliferation of LNCaP cells was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Propofol significantly inhibited DHT-induced expression of androgen receptor target genes in a dose- and time-dependent manner, and immunoblotting and immunofluorescence assays indicated that propofol suppressed nuclear levels of androgen receptor proteins. Exposure to propofol for 24h suppressed the proliferation of LNCaP cells, whereas 4h of exposure did not exert significant effects. Together, our results indicate that propofol suppresses nuclear androgen receptor protein levels, and inhibits androgen receptor transcriptional activity and proliferation in LNCaP cells.
雄激素受体是一种核受体和转录因子，可被雄激素激活。雄激素受体活性在前列腺癌的发生和发展中起着关键作用。尽管越来越多的证据表明包括阿片类药物在内的全身麻醉药会影响癌细胞生长并影响患者预后，但这些药物对前列腺癌中雄激素受体的影响尚不清楚。本研究的目的是探讨全身麻醉药丙泊酚对前列腺癌细胞中雄激素受体活性的影响。用二氢睾酮（DHT）刺激雄激素依赖性人前列腺癌细胞系（LNCaP）并使其暴露于丙泊酚。使用实时逆转录聚合酶链反应研究雄激素受体靶基因的诱导情况，并使用免疫印迹和免疫荧光分析来分析雄激素受体蛋白水平和定位模式。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）分析来分析丙泊酚对LNCaP细胞增殖的影响。丙泊酚以剂量和时间依赖性方式显著抑制DHT诱导的雄激素受体靶基因的表达，免疫印迹和免疫荧光分析表明丙泊酚抑制雄激素受体蛋白的核水平。暴露于丙泊酚24小时可抑制LNCaP细胞的增殖，而暴露4小时则未产生显著影响。总之，我们的结果表明丙泊酚可抑制核雄激素受体蛋白水平，并抑制LNCaP细胞中的雄激素受体转录活性和增殖。
