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二甲基亚砜在睾丸胚胎癌治疗中诱导化疗耐药。

Dimethyl sulfoxide induces chemotherapeutic resistance in the treatment of testicular embryonal carcinomas.

作者信息

Kita Hiroko, Okamoto Keisei, Kushima Ryoji, Kawauchi Akihiro, Chano Tokuhiro

机构信息

Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan ; Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.

Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.

出版信息

Oncol Lett. 2015 Aug;10(2):661-666. doi: 10.3892/ol.2015.3306. Epub 2015 Jun 2.

Abstract

Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is used as a solvent in biological studies and as a vehicle for drug therapy. The present study was designed to evaluate the potential effects of DMSO as a solvent in the treatment of testicular embryonal carcinomas (ECs). DMSO was applied to two human EC cell lines (NEC8 and NEC14), with the treated cells evaluated in relation to cisplatin (CDDP) resistance, differentiation (using Vimentin, Fibronectin, TRA-1-60, and SSEA-1 and -3 as markers) and stemness (denoted by expression of SOX2 and OCT3/4). Furthermore, DNA methyltransferase (DNMT-1, -3A and -3L) expression and methylation status were analyzed. DMSO induced resistance to CDDP, aberrant differentiation and reduction of stemness-related markers in each of the EC cell lines. The expression levels of DNMT-3L and -3A were reduced in response to DMSO, while this treatment also affected DNA methylation. The data demonstrated that DMSO perturbed differentiation, reduced stemness and induced resistance to CDDP in human EC cells. Therefore, DMSO could reduce drug efficacy against EC cells and its use should be carefully managed in the clinical application of chemotherapy.

摘要

二甲基亚砜(DMSO)是一种两亲性分子,在生物学研究中用作溶剂,在药物治疗中用作载体。本研究旨在评估DMSO作为溶剂在治疗睾丸胚胎癌(EC)中的潜在作用。将DMSO应用于两个人类EC细胞系(NEC8和NEC14),并对处理后的细胞进行顺铂(CDDP)耐药性、分化(使用波形蛋白、纤连蛋白、TRA-1-60以及SSEA-1和-3作为标志物)和干性(通过SOX2和OCT3/4的表达表示)方面的评估。此外,还分析了DNA甲基转移酶(DNMT-1、-3A和-3L)的表达及甲基化状态。DMSO诱导了每个EC细胞系对CDDP的耐药性、异常分化以及干性相关标志物的减少。响应DMSO,DNMT-3L和-3A的表达水平降低,同时这种处理也影响了DNA甲基化。数据表明,DMSO扰乱了人类EC细胞的分化,降低了干性,并诱导了对CDDP的耐药性。因此,DMSO可能会降低针对EC细胞的药物疗效,在化疗的临床应用中应谨慎使用。

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