Antineoplastic effect of doxorubizen in vitro in continuous and primary human anaplastic thyroid cancer cells.

IF 3.7 3区医学 Q2 Medicine Endocrine Pub Date : 2024-11-21 DOI:10.1007/s12020-024-04088-5

Giusy Elia, Silvia Martina Ferrari, Iryna Tkachenko, Dipak Walunj, Eugenia Balestri, Chiara Botrini, Francesca Ragusa, Alessandro Antonelli, Gary Gellerman, Poupak Fallahi

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Abstract

Purpose: New drugs are needed for the therapy of anaplastic thyroid cancer (ATC). This study aims to investigate doxorubizen (a dual-action structural hybrid (chimera) of doxorubicin (Dox) and DNA methylating drug temozolomide), in comparison with Dox, and alone or in combination with lenvatinib in ATC 8305C cells, and in primary human ATC cell cultures (pATC).

Methods: We have investigated doxorubizen, Dox, and lenvatinib on 5 different pATC and in continuous 8305C cell line in vitro, evaluating their effect on cells proliferation by WST-1, apoptosis (Hoechst ad Annexin V assays) and migration (Chemicon QCM™ 96-well Migration Assay).

Results: The results have demonstrated: (1) a significant antiproliferative and proapoptotic effect of doxorubizen in 8305C and in pATC; (2) a significant antiproliferative and proapoptotic effect of Dox in pATC, and in 8305C; (3) the antineoplastic effect of lenvatinib in 8305C and in pATC; (4) a stronger antiproliferative and proapoptotic effect of doxorubizen than that of Dox, or lenvatinib; (5) that doxorubizen induced an inhibition of migration in pATC stronger than that of Dox, or lenvatinib; (6) that doxorubizen is able to synergize in vitro with lenvatinib increasing the antiproliferative effect, while doxorubizen alone is the primary factor that promotes the proapoptotic impact.

Conclusion: We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients.

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多柔比增在体外对连续性和原发性人类无性甲状腺癌细胞的抗肿瘤作用。

目的：治疗无性甲状腺癌（ATC）需要新药。本研究旨在研究多柔比增（一种多柔比星（Dox）和DNA甲基化药物替莫唑胺的双效结构混合物（嵌合体））与Dox的比较，以及在ATC 8305C细胞和原代人类ATC细胞培养物（pATC）中单独使用或与来伐替尼联合使用的情况：我们在体外对 5 种不同的 pATC 和连续的 8305C 细胞系进行了多索比增、Dox 和来伐替尼的研究，用 WST-1 评估了它们对细胞增殖、凋亡（Hoechst 和 Annexin V 检测）和迁移（Chemicon QCM™ 96 孔迁移检测）的影响：结果表明(1) 多柔比增在 8305C 和 pATC 中具有明显的抗增殖和促凋亡作用；(2) Dox 在 pATC 和 8305C 中具有明显的抗增殖和促凋亡作用；(3) 来伐替尼在 8305C 和 pATC 中具有抗肿瘤作用；(4) 多柔比增的抗增殖和促凋亡作用强于 Dox 或来伐替尼；(5) 多柔比增对 pATC 迁移的抑制作用强于多柔比增或仑伐替尼；(6) 多柔比增能够在体外与仑伐替尼协同增强抗增殖作用，而单独使用多柔比增则是促进细胞凋亡的主要因素。结论我们首次证明，多柔比增在体外 8305C 和 5 种不同的 pATC 中具有强效抗肿瘤作用，并能与来伐替尼协同作用。这些结果为今后评估多柔比增对 ATC 患者的抗肿瘤作用开辟了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine 医学-内分泌学与代谢

CiteScore

6.40

自引率

5.40%

发文量

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.