Effect of AKT inhibition on epithelial-mesenchymal transition and ZEB1-potentiated radiotherapy in nasopharyngeal carcinoma

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...

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Bibliographic Details
Published inOncology letters Vol. 6; no. 5; pp. 1234 - 1240
Main Authors CHEN, WEIGUO, WU, SIPEI, ZHANG, GONG, WANG, WENJUN, SHI, YONGSHENG
Format Journal Article
LanguageEnglish
Published Greece D.A. Spandidos 01.11.2013
Spandidos Publications UK Ltd
Subjects
AKT kinase inhibitor
AKT/ZEB1 pathway
Brain cancer
Cancer therapies
epithelial-mesenchymal transition
Head & neck cancer
Kinases
Medical prognosis
Metastasis
nasopharyngeal carcinoma
Oncology
Phosphorylation
Radiation therapy
radiotherapy
Studies
Throat cancer
Tumors
United States > US
radiotherapy
nasopharyngeal carcinoma
epithelial-mesenchymal transition
AKT kinase inhibitor
AKT/ZEB1 pathway
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Summary: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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ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2013.1552