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

Chen,Weiguo; Wu,Sipei; Zhang,Gong; Wang,Wenjun; Shi,Yongsheng

doi:10.3892/ol.2013.1552

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

Authors:
- Weiguo Chen
- Sipei Wu
- Gong Zhang
- Wenjun Wang
- Yongsheng Shi
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Affiliations: Department of Liver Disease Medicine, Pingxiang Hospital, Pingxiang, Jiangxi 33700, P.R. China, Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Radiotherapy, Shanxi People's Hospital, Taiyuan, Shanxi 030012, P.R. China, Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: August 29, 2013 https://doi.org/10.3892/ol.2013.1552
Pages: 1234-1240

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Abstract

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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