斑马鱼胚胎癌细胞异种移植作为肾上腺皮质癌药物筛选的实验工具。

IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM
Mariangela Tamburello, Andrea Abate, Sandra Sigala
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引用次数: 0

摘要

尽管在体内实验中广泛使用小鼠模型,但斑马鱼(Danio rerio)提供了独特的优势,使其成为药物筛选的多功能和更快的临床前模型,特别是肾上腺皮质癌(ACC),这是一种罕见的恶性肿瘤,临床前模型有限,反映了患者的异质性。在过去的十年中,细胞系、类器官和小鼠模型等模型取得了重大进展,这对促进疾病的理解和治疗发展至关重要。然而,最近的评论忽视了斑马鱼的ACC模型。这篇迷你综述旨在通过详细介绍斑马鱼模型在ACC研究中的进展来填补这一空白。最近的研究利用异种移植ACC细胞的斑马鱼胚胎作为研究药物对肿瘤生长和转移影响的新方法,与其他肿瘤的研究一致。具体来说,研究证明醋酸阿比特龙、曲比汀和黄体酮在无毒浓度下能显著缩小肿瘤面积。有趣的是,该模型在体内证实了转移来源的细胞能够转移,并且trabectedin和黄体酮降低了转移胚胎的发生率。另一项研究表明,在敲除或抑制G2-044后,H295R/ tr - sf -1异种移植胚胎的转移形成明显减少。尽管存在一些局限性,但斑马鱼异种移植为筛选潜在有效药物、确定剂量毒性和确定最有希望的化合物提供了一个合适和快速的动物模型,用于更高级的临床前阶段,特别是在治疗选择有限的罕见疾病(如ACC)中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cancer cell xenografts in zebrafish embryos as an experimental tool in drug screening for adrenocortical carcinoma.

Despite the widespread use of murine models in in-vivo experiments, the zebrafish (Danio rerio) offers unique advantages that make it a versatile and faster preclinical model for drug screening, particularly for adrenocortical carcinoma (ACC), a rare malignancy with limited preclinical models that reflect patient heterogeneities. Over the past decade, significant progress has been made with models like cell lines, organoids, and murine models, which are crucial for advancing disease understanding and treatment development. However, recent reviews have overlooked zebrafish model for ACC. This mini review aims to fill this gap by detailing the advancements of the zebrafish model in ACC research. Recent studies have utilized zebrafish embryos xenografted with ACC cells as a novel approach to studying drug effects on tumor growth and metastasis, consistent with studies regarding other tumors. Specifically, it was demonstrated the ability of abiraterone acetate, trabectedin and progesterone to significantly reduce the tumor area at non-toxic-concentrations. Interestingly, this model allowed to confirm in vivo that metastasis-derived cells were able to metastasize and that trabectedin and progesterone reduced the rate of embryos with metastasis. One more study showed that metastasis formation was significantly reduced in H295R/TR-SF-1-xenografted embryos after fascin1 knock-out or inhibition with G2-044. Even with some limitations, the zebrafish xenografts offer a suitable and expeditious animal model for the screening of potentially effective drugs, identification of dose toxicity, and determination of the most promising compounds for more advanced preclinical phases, especially in rare diseases with limited therapeutic options such as ACC.

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CiteScore
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