Waszut U, Szyszka P, Dworakowska D
Department of Nuclear Medicine, Medical University of Gdansk, Gdansk, Poland.
Departments of Medicine and Endocrinology, King's College Hospital, London, United Kingdom.
J Physiol Pharmacol. 2017 Feb;68(1):13-26.
Adrenocortical carcinoma is a rare disease with poor prognosis. Mitotane is the most effective agent in post-operative treatment (or when inoperable). It selectively limits growth and bioactivity of adrenal tissue. Despite 60 years of use, the basis for its action has yet to be convincingly established. This review summarizes current knowledge of mitotane effects, based on studies on adrenal tissue and primary cell cultures, with emphasis on more recent studies of cell lines. We consider features of the adrenal cortex that might explain mitotane selectivity, and review effects on non-adrenal cells. Since the most clear-cut mitotane effects have been observed for mitochondria, this topic is the core of the review. Mitochondria present unique characteristics in steroidogenic tissue and are known to be important in malignancy development and apoptosis. We look at the evidence for mitotane activation within mitochondria, its impact on mitochondrial energy metabolism and other cellular processes as well as on downstream effects in the cell, such as apoptosis initiation. Further genomic and proteomic investigative studies are likely to yield useful results.
肾上腺皮质癌是一种预后较差的罕见疾病。米托坦是术后治疗（或无法手术时）最有效的药物。它能选择性地限制肾上腺组织的生长和生物活性。尽管已使用了60年，但其作用机制尚未得到令人信服的确立。本综述基于对肾上腺组织和原代细胞培养的研究，总结了目前关于米托坦作用的知识，重点是对细胞系的最新研究。我们考虑了可能解释米托坦选择性的肾上腺皮质特征，并综述了其对非肾上腺细胞的影响。由于米托坦对线粒体的作用最为明确，因此该主题是综述的核心。线粒体在类固醇生成组织中具有独特的特征，并且已知在恶性肿瘤发展和细胞凋亡中起重要作用。我们研究了米托坦在线粒体内激活的证据，其对线粒体能量代谢和其他细胞过程以及对细胞下游效应（如凋亡启动）的影响。进一步的基因组和蛋白质组学研究可能会产生有用的结果。
