Hong Yao, Beibei Fan, Chuanbao Li, Desheng Chen, Zhuoyi Tang, Jingwei Ye, Weiting Gu, Yijun Cheng, Hao Tang, Shaojian Lin, Li Xue, Yanting Liu, Zhe Bao Wu
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引用次数: 0
Abstract
Context: Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial neuroendocrine tumors. Surgical resection is the first choice for most subtypes of PitNETs. However, radical removal of invasive tumors remains challenging. A novel pharmacological therapy is objectively needed. Sirtuin 6 (Sirt6) is a member of the NAD+-dependent class III deacetylase sirtuin family, which plays a key role in tumorigenesis in many tumors. However, the role of Sirt6 and its activator in PitNETs is still unclear.
Objective: In the study, we investigated the expression of Sirt6 and the antitumor effect of the Sirt6 activator MDL-800 in PitNETs.
Methods: The expression of Sirt6 was detected in PitNET and cell lines by RNA-seq, immunohistochemistry, and western blotting. To test Sirt6 and its activator MDL-800, the cell viability, clone formation, and xenograft experiment were conducted. Autophagy was evaluated by microscopy and western blotting analysis. The efficacy of MDL-800 in the human primary PitNET cells was also investigated by the cell viability assay.
Results: Low expression of Sirt6 was found in PitNET tissues and two pituitary cell lines. Sirt6 inhibited cell proliferation and clone formation. Treatment with MDL-800 suppressed cell growth in vitro and in vivo. Further mechanistic studies showed that MDL-800 could lead to lethal autophagy and exert an antitumor effect in human primary PitNET cells.
Conclusion: Our results suggest that activation of Sirt6 by its selective activator MDL-800 is a promising therapy for PitNETs.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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