Effect of AKT inhibition on epithelial-mesenchymal transition and ZEB1-potentiated radiotherapy in nasopharyngeal carcinoma.
Effect of AKT inhibition on epithelial-mesenchymal transition and ZEB1-potentiated radiotherapy in nasopharyngeal carcinoma.
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DOI：
10.3892/ol.2013.1552
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发表时间：
2013-11
期刊：
影响因子：
2.9
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Chen W;Wu S;Zhang G;Wang W;Shi Y
放射治疗是鼻咽癌（NPC）的主要治疗方案，尽管对完整疗程的放射治疗的初始反应良好，但复发和转移是常见的事件。许多先前的研究已经观察到电离辐射（IR）可以通过上皮-间质转化（EMT）增强癌细胞的迁移和侵袭特性。在本研究中，22例NPC和7例正常病例（仅慢性炎症）的肿瘤队列进行了研究，并证明AKT的表达与ZEB 1的表达呈正相关。IR治疗后，7/10例患者出现复发和转移，此外还出现磷酸化AKT（S473）和ZEB 1的高表达水平。AKT抑制剂GSK 690693可抑制AKT，阻断IR后ZEB 1和vimentin的表达，恢复IR后E-cadherin的表达，从而阻止肿瘤细胞的迁移和EMT。此外，通过GSK 690693抑制AKT显示出在体外和体内显著增加肿瘤细胞对IR的敏感性。这些观察结果表明，GSK 690693可能有助于预防NPC患者IR治疗后的复发和转移。
Radiotherapy is a major treatment regime for nasopharyngeal carcinoma (NPC), and although initial responses to a complete course of radiation are good, recurrence and metastasis are frequent events. A number of previous studies have observed that ionizing radiation (IR) may enhance the migratory and invasive properties of cancer cells through epithelial-mesenchymal transition (EMT). In the present study, a tumor cohort of 22 NPC and 7 normal cases (chronic inflammation only) were investigated and the expression of AKT was demonstrated to positively correlate with the expression of ZEB1. Following treatment with IR, 7/10 patients suffered recurrence and metastasis, in addition to high expression levels of phosphorylated AKT (S473) and ZEB1. The AKT inhibitor, GSK690693, inhibited AKT, blocked the expression of ZEB1 and vimentin and restored the expression of E-cadherin following IR, thus preventing the migration and EMT of the tumor cells. In addition, the inhibition of AKT via GSK690693 was shown to markedly increase the sensitivity of tumor cells to IR in vitro and in vivo. These observations indicate that GSK690693 may aid in the prevention of recurrence and metastasis following IR therapy in NPC patients.
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影响因子：
6.4
作者：
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DOI：
10.1158/1078-0432.ccr-09-1026
发表时间：
2010-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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5.2
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