Zhu Hui-Li, Xie Si-Ming, Fang Mao, Zhang Ji-Jun, Weng Ze-Ping, Zhong Xue-Yun
The First Affiliated Hospital of Jinan University, Guangzhou, China; Department of Pathology, Medical College of Jinan University, Guangzhou, China.
Neuropathology. 2014 Jun;34(3):227-35. doi: 10.1111/neup.12085. Epub 2013 Dec 20.
Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding protein (4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2-BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine (BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma.
耐药性是胶质瘤治疗中最严峻的障碍之一。真核生物翻译起始因子4E结合蛋白（4E-BP1）是蛋白质翻译起始限速步骤中的关键组分，与多种肿瘤类型的不良预后密切相关。然而，4E-BP1是否参与人类胶质瘤的耐药性尚不清楚。在此我们表明，4E-BP1在人SWOZ2-卡莫司汀耐药胶质瘤细胞中的表达显著低于其亲本SWOZ2细胞系。此外，通过短发夹RNA下调4E-BP1可显著削弱SWOZ2和U251细胞对卡莫司汀（BCNU）的敏感性。此外，用质粒转染过表达4E-BP1可恢复这种敏感性。临床研究表明，原发性胶质瘤组织中4E-BP1的表达水平明显高于复发性胶质瘤组织。综上所述，我们的结果表明，4E-BP1是一种导致获得性耐药的新蛋白，它可能是逆转人类胶质瘤耐药性的潜在靶点。
