Radiosensitivity of prostate cancer cells is enhanced by EGFR inhibitor C225

PurposeTo determine the direct effects of the epidermal growth factor receptor (EGFR) inhibitor C225 on the radiosensitivity of human prostate cancer cells.Experimental designHuman prostate cancer DU145 cells were irradiated with ⁶⁰Co (1.953 Gy/min) at various doses in the presence or absence of C225. The cellular proliferation and cell-survival rate were evaluated by MTT and colony-forming assays after irradiation. The cell-cycle distribution, cell apoptosis, and MAPK expression were investigated using FCM. The expression of Cyclin D1, CDK2, CDK4, and Survivin were determined by RT-PCR.ResultsThe RBE in the C225 group compared with that in the control group was 1.39. Cells treated with C225 and irradiated at 4 Gy predominantly exhibited G₀/G₁ phase arrest and significant decrease in the fraction of cells in the S phase in comparison with those in the control cells, respectively. An evidently higher apoptosis rate on irradiation at 4 Gy was observed in C225-treated cells compared with that in the control cells. Decreased cell proliferation and increased cell death were further supported by the down-regulation of cyclin D1, CDK2, CDK4, and survivin in C225-treated DU145 cells, as determined by RT-PCR. Furthermore, C225 significantly inhibited the phosphorylation of P38-MAPK in DU145 cells.ConclusionsThe EGFR inhibitor C225 increased the radiosensitivity of DU145 cells through antiproliferative effect, inhibition of clonal growth, G₀/G₁ phase arrest, apoptosis induction, and inhibition of EGFR-signaling pathways by the down-regulation of MAPK activation.