Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma.
Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma.
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抑制延伸因子 2 激酶可增强替莫唑胺对抗神经胶质瘤的抗肿瘤活性
DOI：
10.1371/journal.pone.0081345
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yang JM
中科院分区：
文献类型：
--
作者：
Liu XY;Zhang L;Wu J;Zhou L;Ren YJ;Yang WQ;Ming ZJ;Chen B;Wang J;Zhang Y;Yang JM
背景多形性胶质母细胞瘤是最常见的一种脑癌，平均生存期不到12个月，是一种高度侵袭性和致命性的疾病，其特征是胶质瘤细胞在最初治疗后存活，并通过脑实质侵袭和破坏正常脑组织，最终对现有治疗方法产生抵抗。替莫唑胺(TMZ)是治疗原发和复发高级别胶质瘤的常用化疗药物。然而，TMZ的治疗效果往往并不令人满意。在这项研究中，我们试图确定EEF-2激酶是否影响胶质瘤细胞对TMZ治疗的敏感性。方法/主要研究结果采用EEF-2激酶的小分子抑制剂RNA干扰方法，在体内外胶质瘤模型中，我们观察到抑制EEF-2激酶可以增强胶质瘤细胞对TMZ的敏感性，并且这种增敏作用与阻断TMZ引起的自噬和促进细胞凋亡有关。结论/意义提示靶向EEF-2激酶可增强TMZ的抗胶质瘤活性，其抑制剂可作为TMZ的化疗增敏剂用于恶性胶质瘤的治疗。
Background Glioblastoma multiforme (GBM), the most common form of brain cancer with an average survival of less than 12 months, is a highly aggressive and fatal disease characterized by survival of glioma cells following initial treatment, invasion through the brain parenchyma and destruction of normal brain tissues, and ultimately resistance to current treatments. Temozolomide (TMZ) is commonly used chemotherapy for treatment of primary and recurrent high-grade gliomas. Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this study, we sought to determine whether eEF-2 kinase affected the sensitivity of glioma cells to treatment with TMZ. Methodology/Principal Findings Using RNA interference approach, a small molecule inhibitor of eEF-2 kinase, and in vitro and in vivo glioma models, we observed that inhibition of eEF-2 kinase could enhance sensitivity of glioma cells to TMZ, and that this sensitizing effect was associated with blockade of autophagy and augmentation of apoptosis caused by TMZ. Conclusions/Significance These findings demonstrated that targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ, and inhibitors of this kinase may be exploited as chemo-sensitizers for TMZ in treatment of malignant glioma.
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影响因子：
3.7
作者：
Cheng Y;Li H;Ren X;Niu T;Hait WN;Yang J
通讯作者：
Yang J
EEF2激酶通过阻止翻译伸长来赋予对营养剥夺的耐药性。
影响因子：
64.5
作者：
Leprivier G;Remke M;Rotblat B;Dubuc A;Mateo AR;Kool M;Agnihotri S;El-Naggar A;Yu B;Somasekharan SP;Faubert B;Bridon G;Tognon CE;Mathers J;Thomas R;Li A;Barokas A;Kwok B;Bowden M;Smith S;Wu X;Korshunov A;Hielscher T;Northcott PA;Galpin JD;Ahern CA;Wang Y;McCabe MG;Collins VP;Jones RG;Pollak M;Delattre O;Gleave ME;Jan E;Pfister SM;Proud CG;Derry WB;Taylor MD;Sorensen PH
通讯作者：
Sorensen PH
DOI：
10.3322/caac.20069
发表时间：
2010-05
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Van Meir EG;Hadjipanayis CG;Norden AD;Shu HK;Wen PY;Olson JJ
通讯作者：
Olson JJ
影响因子：
2.9
作者：
Chen, Y;Matsushita, M;Hallenbeck, JM
通讯作者：
Hallenbeck, JM
EEF2K 对自噬和细胞凋亡的综合调控控制细胞命运并调节姜黄素和万卡迪对抗肿瘤细胞的功效
影响因子：
13.3
作者：
Cheng, Yan;Ren, Xingcong;Yang, Jin-Ming
通讯作者：
Yang, Jin-Ming