Sun Junyan, Wang Dongmei, Guo Lianying, Fang Shengyun, Wang Yang, Xing Rong
Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical UniversityDalian, China; Department of Experimental Functionality, College of Basic Medical SciencesDalian, China.
College of Integrative Medicine, Dalian Medical University Dalian, China.
Front Neurosci. 2017 Mar 7;11:116. doi: 10.3389/fnins.2017.00116. eCollection 2017.
Neuroblastoma is the most common extracranial tumors in children. At present about the true etiology of neuroblastoma is unclear and many studies have tried to find effective treatments for these primary malignant tumors. Although it has been illustrated that androgen receptor (AR) was expressed in neuroblastoma cells in some former reports, the biological role of androgen receptor in the development of neuroblastoma is not fully understood. Androgen (R1881) and the antagonists of androgen receptor (MDV3100 and ARN509) were used to study the role of the androgen receptor signaling pathway and on SH-SY5Y and Neuro-2a (N2a) cell lines. We found that AR expression showed an R1881 dose-dependent manner in neuroblastoma cells and R1881was able to increase, while both antagonists of androgen receptor (MDV3100 and ARN509) significantly decrease, the proliferation, migration, invasion and sphere formation of SH-SY5Y and N2a cells. Moreover, androgen promoted the growth of N2a tumor . However, when androgen receptor (AR) was effectively knocked down in the two cell lines by siRNA, either promoting or inhibiting effect of the androgen or androgen receptor antagonists, respectively, was attenuated. Our results suggested that androgen receptor may involve in the progression of neuroblastoma as well as provided insight into a new target for the diagnosis and treatment of neuroblastoma patients.
神经母细胞瘤是儿童最常见的颅外肿瘤。目前,神经母细胞瘤的真正病因尚不清楚,许多研究试图找到针对这些原发性恶性肿瘤的有效治疗方法。尽管在一些先前的报道中已表明雄激素受体(AR)在神经母细胞瘤细胞中表达,但雄激素受体在神经母细胞瘤发生发展中的生物学作用尚未完全明确。使用雄激素(R1881)以及雄激素受体拮抗剂(MDV3100和ARN509)来研究雄激素受体信号通路在SH-SY-5Y和Neuro-2a(N2a)细胞系中的作用。我们发现,在神经母细胞瘤细胞中AR表达呈R1881剂量依赖性,R1881能够促进SH-SY-5Y和N2a细胞的增殖、迁移、侵袭及成球能力,而雄激素受体拮抗剂(MDV3100和ARN509)则显著降低这些能力。此外,雄激素促进N2a肿瘤生长。然而,当通过小干扰RNA(siRNA)在这两种细胞系中有效敲低雄激素受体(AR)时,雄激素或雄激素受体拮抗剂的促进或抑制作用分别减弱。我们的结果表明,雄激素受体可能参与神经母细胞瘤的进展,也为神经母细胞瘤患者的诊断和治疗提供了一个新靶点。