Role of asparagine synthetase in doxorubicin-induced resistance

Biomarkers and Genomic Medicine Pub Date : 2013-09-01 DOI:10.1016/j.bgm.2013.07.003

Li-Hsun Lin , Szu-Ting Lin , Hsiu-Chuan Chou

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引用次数: 4

Abstract

Research has shown drug resistance as the major cause of failure of cancer chemotherapy. In this study, doxorubicin-sensitive human uterine cancer cell (hUCC) MES/SA, as well as doxorubicin-resistant hUCC MES/SA-DxR 2μM and MES/SA-DxR 8μM were used. Subsequently, asparagine synthetase (ASNS), a protein that had previously been proposed to be a putative cancer drug target in our laboratory, was silenced by siRNA knockdown to study the mechanism of doxorubicin-induced resistance further. After potent knockdown of ASNS, cell viability in two doxorubicin-resistant cell lines MES/SA-DxR 2μM and MES/SA-DxR 8μM was decreased, as indicated by an MTT cell proliferation assay. By coupling two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, proteins that play a vital role in ASNS signaling network and development of doxorubicin-induced resistance were identified. Among all the proteins that we have identified, GRP78 and AKR1C1 appear to be involved in drug resistance, replication factor C appears to participate in DNA repairing, and PP6C is proposed to play a role in cell cycle arrest.

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天冬酰胺合成酶在阿霉素诱导耐药中的作用

研究表明，耐药性是癌症化疗失败的主要原因。本研究采用对阿霉素敏感的人子宫癌细胞(hUCC) MES/SA，以及对阿霉素耐药的hUCC MES/SA- dxr 2μM和MES/SA- dxr 8μM。随后，我们实验室通过敲低siRNA沉默了先前被认为是癌症药物靶点的蛋白天冬酰胺合成酶(ASNS)，进一步研究了阿霉素诱导耐药的机制。MTT细胞增殖实验显示，ASNS有效敲除后，两株抗阿霉素细胞系MES/SA-DxR 2μM和MES/SA-DxR 8μM的细胞活力下降。通过二维凝胶电泳和基质辅助激光解吸电离飞行时间质谱联用，鉴定了在ASNS信号网络和阿霉素诱导耐药发展中起重要作用的蛋白质。在我们鉴定的所有蛋白中，GRP78和AKR1C1似乎参与了耐药，复制因子C似乎参与了DNA修复，PP6C被认为在细胞周期阻滞中发挥作用。

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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Biomarkers and Genomic Medicine

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