Radiosensitivity of prostate cancer cells is enhanced by EGFR inhibitor C225

Purpose: To determine the direct effects of the epidermal growth factor receptor (EGFR) inhibitor C225 on the radiosensitivity of human prostate cancer cells. Experimental design: Human prostate cancer DU145 cells were irradiated with Co-60 (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. Results: The 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 GIG, 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. Conclusions: The EGER inhibitor C225 increased the radiosensitivity of DU145 cells through antiproliferative effect, inhibition of clonal growth, G(0)/G(1) phase arrest, apoptosis induction, and inhibition of EGFR-signaling pathways by the down-regulation of MAPK activation. (C) 2010 Published by Elsevier Inc.