Culig Zoran
Experimental Urology, Department of Urology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Cancers (Basel). 2021 Jun 12;13(12):2944. doi: 10.3390/cancers13122944.
Non-steroidal anti-androgens have a major role in the treatment of non-localized prostate cancer. Interleukins are involved in the regulation of many cellular functions in prostate cancer and also modify cellular response to anti-androgens. A specific role of selected IL is presented in this review. IL-8 is a cytokine expressed in prostate cancer tissue and microenvironment and promotes proliferation and androgen receptor-mediated transcription. In contrast, IL-1 displays negative effects on expression of androgen receptor and its target genes. A subgroup of prostate cancers show neuroendocrine differentiation, which may be in part stimulated by androgen ablation. A similar effect was observed after treatment of cells with IL-10. Another cytokine which is implicated in regulation of androgenic response is IL-23, secreted by myeloid cells. Most studies on androgens and IL were carried out with IL-6, which acts through the signal transducer and activator of the transcription (STAT) factor pathway. IL-6 is implicated in resistance to enzalutamide. Activation of the STAT-3 pathway is associated with increased cellular stemness. IL-6 activation of the androgen receptor in some prostate cancers is associated with increased growth in vitro and in vivo. Molecules such as galiellalactone or niclosamide have an inhibitory effect on both androgen receptor and STAT-3 pathways.
非甾体类抗雄激素药物在非局限性前列腺癌的治疗中发挥着重要作用。白细胞介素参与前列腺癌多种细胞功能的调节，还会改变细胞对抗雄激素药物的反应。本综述介绍了特定白细胞介素的具体作用。白细胞介素-8是一种在前列腺癌组织和微环境中表达的细胞因子，可促进增殖以及雄激素受体介导的转录。相比之下，白细胞介素-1对雄激素受体及其靶基因的表达具有负面影响。一部分前列腺癌表现出神经内分泌分化，这可能部分是由雄激素剥夺刺激所致。用白细胞介素-10处理细胞后也观察到了类似的效果。另一种与雄激素反应调节有关的细胞因子是由髓样细胞分泌的白细胞介素-23。大多数关于雄激素和白细胞介素的研究是针对白细胞介素-6进行的，它通过信号转导和转录激活因子（STAT）途径发挥作用。白细胞介素-6与恩杂鲁胺耐药有关。STAT-3途径的激活与细胞干性增加有关。在一些前列腺癌中，白细胞介素-6对雄激素受体的激活与体内外生长增加有关。诸如加列内酯或氯硝柳胺等分子对雄激素受体和STAT-3途径均有抑制作用。
