吉非替尼不同加药时间肺癌A549细胞放射增敏研究

目的 探讨吉非替尼不同加药时间对离体培养肺癌细胞系A549的放射增敏效应的影响.方法 实验分吉非替尼照前24 h加药组、照后即刻加药组、照后24 h加药组.用克隆形成法检测细胞存活分数,流式细胞仪检测细胞凋亡和细胞周期分布,蛋白免疫印迹检测p21、Cdc25e、Bcl-2、Bax、Rad51和phospho-DNA-PK蛋白表达.结果 吉非替尼照前组、照射即刻加药和照后加药组的放射增敏比(D_0值比)分别为2.23、1.51和1.30.照前加药组观察到更高的凋亡率和G_2+M期阻滞.p21、Cdc25c、Bcl-2、Bax、Rad51和phospho-DNA-PK蛋白表达的改变也较其他组明显.结论 吉非替尼照前加药、照射即刻加药和照后加药对肺癌细胞系A549均有放射增敏效应,但照前加药的效应最强.

Gefitinib at different administration time in radiosensitizing lung adenocarcinoma cells in vitro

Objective To investigate the radiosensitizing effects of gefitinib at different administration time. Methods Gefitinib was administered to A549 lung cancer cells in three different ways (method 1, 24 h before irradiation ;method 2, upon irradiation and method 3, 24 h after irradiation). Cell-surviving rates were evaluated by the colony-forming assays. Cell apoptnsis and cell-cycle distributions were detected by the flow cytometry (FCM). Protein expression of p21, Cdc25c, Bcl-2, Bax, Rad51 and phosphorylated DNA - PKcs (phnspho - DNA - PK) were measured with the Western blot analysis. Results The sensitizing effect ratio (ratio of D_0 value) was 2.23, 1.51 and 1.30 with method 1, 2 and 3, respectively. A higher apoptosis rate and more G_2/M phase arrest were observed with method 1 when compare with method 2 or 3. With the similar tendency, the protein level of p21, Cdc25c, Bcl-2, Bax, RadSl and phospho-DNA-PK changed distinctly. Conclusions Radiosensitizing effects are obtained in all three methods, with gefitinib delivered before irradiation being the best.