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用一种硒铂化合物进行治疗可通过线粒体信号通路诱导T细胞急性淋巴细胞白血病/淋巴瘤细胞凋亡。

Treatment with a selenium-platinum compound induced T-cell acute lymphoblastic leukemia/lymphoma cells apoptosis through the mitochondrial signaling pathway.

作者信息

Wu Feifei, Cao Wei, Xu Huaping, Zhu Mingxia, Wang Jing, Ke Xiaoyan

机构信息

Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China.

Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084, P.R. China.

出版信息

Oncol Lett. 2017 Mar;13(3):1702-1710. doi: 10.3892/ol.2017.5666. Epub 2017 Feb 1.

Abstract

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive hematological disorder that is sensitive to chemotherapy; however, it exhibits frequent relapse rates. Platinum-containing therapeutics are the first-line salvage regimens used in the treatment of relapsed or refractory T-ALL/LBL. The selenium-platinum compound EG-Se/Pt is obtained from the combination of selenium-containing molecules (EG-Se) with cisplatin (CDDP); however, its anticancer properties have been poorly investigated. In the present study, the Cell Counting Kit-8 assay was used to evaluate the inhibitory effect of treatment with EG-Se/Pt on cell viability. Cell cycle distribution, apoptosis, reactive oxygen species (ROS) content and the mitochondrial membrane potential were analyzed using flow cytometry. Intracellular platinum content was detected using inductively coupled plasma mass spectrometry. Caspase activity was determined using a colorimetric assay. The expression of several proteins associated with apoptosis was analyzed using western blotting. The results of the present study demonstrated that treatment with EG-Se/Pt increased the inhibition of Jurkat and Molt-4 T-ALL/LBL cell viability compared with CDDP, and induced apoptosis and cell cycle arrest. The intracellular platinum content of T-ALL/LBL cells treated with EG-Se/Pt was increased compared with that of T-ALL/LBL cells treated with CDDP. EG-Se/Pt-induced apoptosis was mediated by caspase and ROS levels through the activation of the mitochondrial signaling pathway. The results of the present study suggest that EG-Se/Pt is a potential therapeutic candidate for the treatment of T-ALL/LBL.

摘要

T细胞急性淋巴细胞白血病/淋巴瘤(T-ALL/LBL)是一种侵袭性血液系统疾病,对化疗敏感;然而,其复发率很高。含铂疗法是用于治疗复发或难治性T-ALL/LBL的一线挽救方案。硒-铂化合物EG-Se/Pt是由含硒分子(EG-Se)与顺铂(CDDP)结合而成;然而,其抗癌特性尚未得到充分研究。在本研究中,使用细胞计数试剂盒-8检测法评估EG-Se/Pt处理对细胞活力的抑制作用。使用流式细胞术分析细胞周期分布、凋亡、活性氧(ROS)含量和线粒体膜电位。使用电感耦合等离子体质谱法检测细胞内铂含量。使用比色法测定半胱天冬酶活性。使用蛋白质印迹法分析几种与凋亡相关的蛋白质的表达。本研究结果表明,与CDDP相比,EG-Se/Pt处理增强了对Jurkat和Molt-4 T-ALL/LBL细胞活力的抑制作用,并诱导了凋亡和细胞周期停滞。与用CDDP处理的T-ALL/LBL细胞相比,用EG-Se/Pt处理的T-ALL/LBL细胞的细胞内铂含量增加。EG-Se/Pt诱导的凋亡是通过线粒体信号通路的激活由半胱天冬酶和ROS水平介导的。本研究结果表明,EG-Se/Pt是治疗T-ALL/LBL的潜在治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c31/5403366/1643301c8e25/ol-13-03-1702-g00.jpg

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