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

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.