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The different radiosensitivity when combining erlotinib with radiation at different administration schedules might be related to activity variations in c-MET-PI3K-AKT signal transduction

Authors Zhuang H, Bo Q, yuan Z, Wang J, Zhao L, Wang P

Received 26 February 2013

Accepted for publication 15 April 2013

Published 28 May 2013 Volume 2013:6 Pages 603—608


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Hong-Qing Zhuang,1,* Qi-Fu Bo,2,* Zhi-Yong Yuan,1 Jun Wang,1 Lu-Jun Zhao,1 Ping Wang1

1Department of Radiotherapy, Tianjin Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People’s Republic of China; 2Department of Anatomy, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China

*These authors contributed equally to this work

Objectives: The aim of this paper was to investigate the efficacy and activity variation associated with phosphoinositide 3-kinase (PI3K) signal transduction when combining erlotinib with radiation, using different administration schedules.
Materials and methods: Erlotinib was delivered to A973 cancer cells in the following three ways: (1) irradiation after administration, (2) irradiation upon administration, and, (3) irradiation before administration. The cell-survival rates were detected using colony-forming assays, while cell apoptosis was detected with flow cytometry. The expression levels of C-MET, p-C-MET, AKT, and p-AKT were determined via Western blotting analysis, under 6 Gy irradiation with/without erlotinib.
Results: The sensitizer enhancement ratios (SERs) of erlotinib irradiation after administration, irradiation upon administration, and irradiation before administration groups were 2.19, 1.53, and 1.38, respectively. A higher apoptosis rate was observed when irradiation was delivered after erlotinib. In addition, changes in cell apoptosis were found to be related to concurrent changes in C-MET, p-C-MET, AKT, and p-AKT expression. Protein expression increased in the combination groups, with trends showing a negative relationship with cell apoptosis.
Conclusion: The radiosensitive effect of erlotinib varied because of the different administration schedules; this variation may be related to PI3K signal transduction and its associated regulating effect.

Keywords: tyrosine kinase inhibitor, radiosensitization effects, erlotinb, PI3K

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