Radiosensitivity of prostate cancer cells is enhanced by EGFR inhibitor C225.
OBJECTIVE
To determine the direct effects of the epidermal growth factor receptor (EGFR) inhibitor C225 on the radiosensitivity of human prostate cancer cells.


METHODS
Human prostate cancer DU145 cells were irradiated with (60)Co (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 G(0)/G(1) 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 EGFR 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.
Liu
Feng
F
Cancer Center, Peking University Third Hospital, Beijing, China.
Wang
Jun-Jie
JJ
You
Zhen-Yu
ZY
Zhang
Ying-Dong
YD
Zhao
Yong
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D011836:Radiation Tolerance / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab