TAZ promotes temozolomide resistance by upregulating MCL-1 in human glioma cells
TAZ promotes temozolomide resistance by upregulating MCL-1 in human glioma cells
复制标题
TAZ 通过上调人胶质瘤细胞中的 MCL-1 促进替莫唑胺耐药
DOI：
10.1016/j.bbrc.2015.05.115
复制
发表时间：
2015-08-07
影响因子：
3.1
通讯作者：
Li, Zhaoming
中科院分区：
文献类型：
--
作者：
Tian, Tian;Li, Aimin;Li, Zhaoming
替莫唑胺是一种新型细胞毒药物，目前用作多形性胶质母细胞瘤（GBM）的一线化疗。然而，对替莫唑胺的内在或获得性化学耐药性仍然是成功治疗人类 GBM 的最大障碍。造成这种抵抗的主要机制在很大程度上尚不清楚。在本研究中，我们发现神经胶质瘤细胞中具有PDZ结合基序（TAZ）的转录共激活因子的表达与人神经胶质瘤细胞中的替莫唑胺化疗耐药性相关。 TAZ 的过表达促进了 U-87MG 细胞中的替莫唑胺耐药性，而 TAZ 表达的敲低则使替莫唑胺耐药的 U-251 MG 细胞对替莫唑胺敏感。此外，TAZ 通过上调 MCL-1（骨髓细胞白血病 1）抑制替莫唑胺诱导的细胞凋亡，TAZ 的高表达预示着 GBM 患者的不良预后。总之，我们的结果表明，TAZ 在神经胶质瘤细胞对替莫唑胺的耐药性中发挥着关键作用，它可能为改善替莫唑胺耐药性神经胶质瘤的治疗结果提供一个有希望的靶点。 (C) 2015 Elsevier Inc. 保留所有权利。
Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). However, intrinsic or acquired chemoresistance to temozolomide remains the greatest obstacle to the successful treatment of human GBM. The principal mechanism responsible for this resistance is largely unknown. In the present study, we showed that expression of transcriptional coactivator with PDZ-binding motif (TAZ) in glioma cells correlated with temozolomide chemoresistance in human glioma cells. Overexpression of TAZ promoted temozolomide resistance in U-87MG cells, whereas knockdown of TAZ expression sensitized temozolomide-resistant U-251 MG cells to temozolomide. Further, TAZ inhibits temozolomide induced apoptosis via upregulation of MCL-1 (myeloid cell leukemia 1) and high expression of TAZ predicts a poor prognosis for GBM patients. In conclusion, our results suggest that TAZ had a critical role in the resistance to temozolomide in glioma cells, and it may provide a promising target for improving the therapeutic outcome of temozolomide-resistant gliomas. (C) 2015 Elsevier Inc. All rights reserved.