Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling
Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling
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DOI：
10.1016/j.canlet.2011.12.043
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发表时间：
2012-06-01
期刊：
影响因子：
9.7
通讯作者：
Aoyagi, Yutaka
中科院分区：
文献类型：
--
作者：
Fujimaki, Shun;Matsuda, Yasunobu;Aoyagi, Yutaka
索拉非尼是一种适用于肝细胞癌（HCC）的多激酶抑制剂，但其疗效有限是一个亟待解决的问题。在这里，我们表明，共济失调毛细血管扩张突变（ATM）的封锁提高索拉非尼的抗肿瘤作用。当肝癌细胞系HepG 2和PLC/PRF/5被索拉非尼联合ATM小抑制RNA处理时，ATM抑制剂KU 55933或咖啡因，Akt信号被抑制，细胞毒性作用显著增强。此外，ATM抑制有效地抑制索拉非尼诱导的细胞迁移。总之，ATM活性的操纵可能是一个有用的策略，提高索拉非尼治疗肝癌。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Sorafenib is a multi-kinase inhibitor applicable to hepatocellular carcinoma (HCC), but its limited therapeutic effects are a major problem to be solved. Here, we show that blockade of ataxia telangiectasia mutated (ATM) improves the antitumor effects of sorafenib. When hepatoma cell lines HepG2 and PLC/PRF/5 were treated with sorafenib plus ATM small inhibitory RNAs. ATM inhibitor KU55933 or caffeine, Akt signaling was suppressed and the cytotoxic effects were significantly potentiated. Moreover, ATM inhibition effectively suppressed the sorafenib-induced cell migration. Taken together, manipulation of ATM activity might be a useful strategy for improving sorafenib treatment of HCC. (c) 2012 Elsevier Ireland Ltd. All rights reserved.