Department of Obstetrics and Gynecology, Kyorin University Faculty of Medicine, 6-20-2, Shinkawa, Mitaka-city, Tokyo, 181-8611, Japan.
Department of Pharmacology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Hum Cell. 2021 Mar;34(2):394-399. doi: 10.1007/s13577-020-00465-0. Epub 2021 Jan 2.
Dienogest (DNG), is an effective and widely used progestin used in the treatment of endometriosis, yet clinically, a subset of cases show resistance to DNG treatment. During a previous investigation on the effect of DNG of cytokines and growth factor production, we incidentally found that endometriotic cyst fluid did not demonstrate inhibitory effects to DNG in a subset of cases. To clarify the mechanisms of this resistance to DNG, we performed proteomics analysis to compare the protein expression between DNG-sensitive and resistant cases. Based upon our results, several proteins were extracted that relate to neutrophil granulocyte activation marker (myeloperoxidase, lactotransferrin), inflammation (azurocidin, neutrophil gelatinase-associated lipocalin, etc.), and others biological processes reflecting the clinical environment of the endometriotic cyst. Among these proteins, azurocidin (AZU) is perhaps most interesting one as azurocidin is a protease that cleaves insulin-like growth factor-1 (IGFBP-1) associated with clear cell carcinoma of the ovary. We propose that the proteins extracted in the present study warrant further investigation in their relationship to carcinogenesis of endometrioma.
地诺孕素（DNG）是一种有效的、广泛应用于子宫内膜异位症治疗的孕激素，但临床上有一部分病例对 DNG 治疗有抵抗。在之前关于 DNG 对细胞因子和生长因子产生的影响的研究中，我们偶然发现，在一部分病例中，子宫内膜异位囊肿液对 DNG 没有抑制作用。为了阐明这种对 DNG 抵抗的机制，我们进行了蛋白质组学分析，比较了 DNG 敏感和抵抗病例之间的蛋白质表达。根据我们的结果，提取了一些与中性粒细胞粒细胞激活标志物（髓过氧化物酶、乳转铁蛋白）、炎症（天青杀素、中性粒细胞明胶酶相关脂质运载蛋白等）以及反映子宫内膜异位囊肿临床环境的其他生物学过程相关的蛋白质。在这些蛋白质中，天青杀素（AZU）可能是最有趣的一种，因为天青杀素是一种蛋白酶，可切割与卵巢透明细胞癌相关的胰岛素样生长因子结合蛋白-1（IGFBP-1）。我们提出，本研究中提取的蛋白质值得进一步研究其与子宫内膜瘤癌变的关系。
