Downregulation of key regulatory proteins in androgen dependent prostate tumor cells by oncolytic reovirus.
Downregulation of key regulatory proteins in androgen dependent prostate tumor cells by oncolytic reovirus.
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溶瘤呼肠孤病毒下调雄激素依赖性前列腺肿瘤细胞中的关键调节蛋白。
DOI：
10.1016/j.virol.2015.07.007
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Miller,CathyL
中科院分区：
文献类型：
--
作者：
Gupta-Saraf,Pooja;Meseke,Tyler;Miller,CathyL
由于前列腺肿瘤细胞的生长依赖于激素，雄激素消融是前列腺癌(PCa)的有效治疗方法。然而，前列腺癌细胞向雄激素非依赖性生长的进展(去势耐受前列腺癌，CRPC)会导致复发和死亡。缺氧是一种低氧微环境，可以改变包括雄激素受体(AR)在内的PCA调节蛋白的活性，在CRPC的发展过程中起着关键作用。针对缺氧和AR的治疗可以延长CRPC进展的时间，从而延长PCa患者的生存时间。哺乳动物正病毒(MRV)在体内外治疗前列腺癌方面显示出良好的前景。在这项研究中，我们发现MRV感染诱导CRPC进程中相关蛋白的下调，干扰低氧诱导的AR活性，并诱导雄激素依赖细胞的凋亡。这表明MRV具有可被利用来创造抑制进展到CRPC的新疗法的特征。
As prostate tumor cell growth depends on hormones, androgen ablation is an effective therapy for prostate cancer (PCa). However, progression of PCa cells to androgen independent growth (castrate resistant prostate cancer, CRPC) results in relapse and mortality. Hypoxia, a microenvironment of low oxygen that modifies the activity of PCa regulatory proteins including the androgen receptor (AR), plays a critical role in progression to CRPC. Therapies targeting hypoxia and the AR may lengthen the time to CRPC progression thereby increasing survival time of PCa patients. Mammalian Orthoreovirus (MRV) has shown promise for the treatment of prostate tumorsin vitroandin vivo. In this study, we found that MRV infection induces downregulation of proteins implicated in CRPC progression, interferes with hypoxia-induced AR activity, and induces apoptosis in androgen dependent cells. This suggests MRV possesses traits that could be exploited to create novel therapies for the inhibition of progression to CRPC.