Wang Xin, Liu Tianzhu, Bai Yifeng, Liao Hongzhan, Qiu Shengcong, Chang Zhenhua, Liu Yanting, Yan Xiaohui, Guo Hongbo
The National Key Clinic Specialty, the Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, P. R. China; Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, P. R. China.
The National Key Clinic Specialty, the Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, P. R. China.
PLoS One. 2014 Apr 18;9(4):e93439. doi: 10.1371/journal.pone.0093439. eCollection 2014.
This study is to investigate if polymerase I and transcript release factor (PTRF) acts as a modulator in glioblastoma (GBM) chemoresistance.
Multidrug resistant (MDR) GBM cell line U251AR was established by exposing the U251 cell line to imatinib. The 2D-DIGE and MALDI-TOF/TOF-MS were performed on U251 and U251AR cell lines to screen MDR-related proteins. The expression of PTRF was determined by Western blot and quantitative RT-PCR analyses.
When compared with the parental U251 cells, expression of 21 proteins was significantly altered in U251AR cells. Among the 21 differentially expressed proteins, the expression of PTRF was up-regulated by 2.14 folds in U251AR cells when compared with that in the parental U251 cells. Knockdown of PTRF in GBM cell lines significantly increased chemosensitivity of cells to various chemical drugs and decreased the expression levels of caveolin1, a major structural component of caveolae. Expression levels of PTRF and caveolin1 were significantly up-regulated in the relapsed GBM patients. The mRNA level of PTRF and caveolin1 showed a positive correlation in the same GBM specimens.
Our results indicate that PTRF acts as a modulator in GBM chemoresistance.
本研究旨在探究聚合酶I和转录释放因子（PTRF）是否在胶质母细胞瘤（GBM）化疗耐药中发挥调节作用。
通过将U251细胞系暴露于伊马替尼来建立多药耐药（MDR）GBM细胞系U251AR。对U251和U251AR细胞系进行二维差异凝胶电泳（2D-DIGE）和基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF-MS）以筛选与MDR相关的蛋白质。通过蛋白质免疫印迹法（Western blot）和定量逆转录聚合酶链反应（qRT-PCR）分析来测定PTRF的表达。
与亲代U251细胞相比，U251AR细胞中有21种蛋白质的表达发生了显著变化。在这21种差异表达的蛋白质中，与亲代U251细胞相比，U251AR细胞中PTRF的表达上调了2.14倍。在GBM细胞系中敲低PTRF可显著增加细胞对各种化学药物的化疗敏感性，并降低小窝蛋白1（一种小窝的主要结构成分）的表达水平。在复发的GBM患者中，PTRF和小窝蛋白1的表达水平显著上调。在同一GBM标本中，PTRF和小窝蛋白1的mRNA水平呈正相关。
我们的结果表明，PTRF在GBM化疗耐药中发挥调节作用。
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