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舍曲林重新定位:经过四十年肿瘤逆转研究后其作为化疗药物潜在用途的概述。

Sertraline repositioning: an overview of its potential use as a chemotherapeutic agent after four decades of tumor reversal studies.

作者信息

Baú-Carneiro João Luiz, Akemi Guirao Sumida Isabela, Gallon Malu, Zaleski Tânia, Boia-Ferreira Marianna, Bridi Cavassin Francelise

机构信息

Medical School Undergraduate Program, Faculdades Pequeno Príncipe (FPP), Curitiba, Brazil.

Faculty of Medical Sciences, Faculdades Pequeno Príncipe (FPP), Curitiba, Brazil; Faculty of Biological Sciences, Universidade Estadual do Paraná (UNESPAR), Paranaguá, Brazil; Post Graduate Program of National Network's in Education, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.

出版信息

Transl Oncol. 2022 Feb;16:101303. doi: 10.1016/j.tranon.2021.101303. Epub 2021 Dec 12.

Abstract

Sertraline hydrochloride is a first-line antidepressant with potential antineoplastic properties because of its structural similarity with other drugs capable to inhibit the translation-controlled tumor protein (TCTP), a biomolecule involved in cell proliferation. Recent studies suggest it could be repositioned for cancer treatment. In this review, we systematically map the findings that repurpose sertraline as an antitumoral agent, including the mechanisms of action that support this hypotesis. From experimental in vivo and in vitro tumor models of thirteen different types of neoplasms, three mechanisms of action are proposed: apoptosis, autophagy, and drug synergism. The antidepressant is able to inhibit TCTP, modulate chemotherapeutical resistance and exhibit proper cytotoxicity, resulting in reduced cell counting (in vitro) and shrunken tumor masses (in vivo). A mathematical equation determined possible doses to be used in human beings, supporting that sertraline could be explored in clinical trials as a TCTP-inhibitor.

摘要

盐酸舍曲林是一种一线抗抑郁药,因其与其他能够抑制翻译控制肿瘤蛋白(TCTP,一种参与细胞增殖的生物分子)的药物结构相似而具有潜在的抗肿瘤特性。最近的研究表明,它可被重新用于癌症治疗。在本综述中,我们系统地梳理了将舍曲林重新用作抗肿瘤药物的研究结果,包括支持这一假说的作用机制。从13种不同类型肿瘤的体内和体外实验肿瘤模型来看,提出了三种作用机制:细胞凋亡、自噬和药物协同作用。这种抗抑郁药能够抑制TCTP,调节化疗耐药性并表现出适当的细胞毒性,导致细胞计数减少(体外)和肿瘤块缩小(体内)。一个数学方程式确定了可能用于人类的剂量,支持舍曲林可作为TCTP抑制剂在临床试验中进行探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2eb/8681026/229da6670295/ga1.jpg

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