EGFR抑制剂C225对人前列腺癌细胞的放射增敏作用

Radiosensitization effect of EGFR inhibitor C225 on prostate cancer cell

目的探讨表皮生长因子抑制剂C225对人前列腺癌细胞株（DU145）放射敏感性的影响。方法实验组用表皮生长因子抑制剂C225（100nmol／L）处理后，^60Coγ射线（吸收剂量率1．953Gy／min）对体外培养的DU145细胞进行0、2、4、6和8Gy照射，用MTT法、集落形成法检测细胞增殖和细胞存活率；用单击多靶模型拟合剂量存活曲线；用流式细胞仪检测细胞周期和凋亡。结果C225对照射后DU145细胞增殖有明显抑制作用。C225组的放射生物学参数值（D0、Dq、N、SF2）较对照组低。C225组和对照组的RBE比值为1．39。C225组处于S期的细胞比例降低，出现明显的G0／G1期阻滞。C225组细胞的早期凋亡率在照射剂量达4Gy后明显高于对照组（t=-14．55，P〈0．05）。结论表皮生长因子抑制剂C225通过抑制细胞增殖、G0/G1期阻滞和诱导凋亡来增加人前列腺癌细胞放射敏感性。

Objective To determine the effects of EGFR inhibitor C225 on radiosensitivity of human prostate cancer cells. Methods Human prostate cancer DU145 cells were irradiated with ^60 Co （1. 953 Gy/min） at various doses of 0,2,4,6,8 Gy in the presence or absence of C225 （100 nmol/L）. The cellular proliferation and cell surviving rate were evaluated by MTT and the colony-forming assay. The cell cycle distribution and cell apoptosis were tested by flow cytometry. Results C225 caused significant anti-proliferative effect on irradiated DU145 ceils. The radiobiological parameters of C225 group, including D0 , Dq, N, SF2 , were lower than those of control group. The RBE for C225 group compared with control group is 1.39. Cells treated with C225 showed significant G0/G1 phase arrest and a decrease in S phase over the dose of 4 Gy in comparison with the control. Higher apoptosis rate over 4 Gy was observed in C225-treated cells compared to the control （ t = - 14,55, P 〈 0.05）. Conclusions EGFR inhibitor C225 could increase the radiosensitivity of DU145 cells through anti- proliferation, G0/G1 phase arrest and apoptosis induction.