Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors
Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors
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DOI：
10.1016/j.canlet.2011.06.005
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发表时间：
2011-12-01
期刊：
影响因子：
9.7
通讯作者：
Yen, Yun
中科院分区：
文献类型：
--
作者：
Gaur, Shikha;Chen, Linling;Yen, Yun
本研究旨在研究mTOR抑制剂在恢复阿霉素/顺铂化疗敏感性中的可能作用并阐明其潜在机制。阿霉素/顺铂联合托瑞塞尔对人口咽癌细胞株KB及其多药耐药亚克隆KB/7 D的增殖有协同抑制作用。联合阿霉素和托瑞塞尔抑制4 EBP-1和p70 S6 K的磷酸化，参与mTOR通路的蛋白，增加指示DNA损伤的γ H2 AX的表达，触发细胞周期停滞在G2/M和凋亡。我们的结论是，DNA损伤导致的染色质去凝聚为torisel阻断DNA修复所必需的蛋白质的翻译提供了一个简单的途径，从而恢复了化疗敏感性。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The present study was performed to investigate the possible role of mTOR inhibitors in restoring chemosensitivity to adriamycin/cisplatin and elucidate the underlying mechanism. Combining adriamycin/cisplatin with torisel synergistically inhibited the cell proliferation in human oropharyngeal carcinoma cell line KB and its multidrug-resistant subclone KB/7D. Combining adriamycin and torisel inhibited the phosphorylation of 4EBP-1 and p70S6 K, the proteins involved in mTOR pathway, increased expression of gamma H2AX indicative of DNA damage, triggered cell cycle arrest at G2/M and apoptosis. We conclude that chromatin decondensation by DNA damage provided an easy access for torisel to block the translation of proteins essential for DNA repair thereby restoring the chemosensitivity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.