吉西他滨对非小细胞肺癌细胞株A-549放疗增敏的机制

Radiosensitivity Mechanism of Gemcitabine on the Non-small Cell Lung Cancer Cell Line A-549

目的:研究吉西他滨(GEM)对体外培养非小细胞肺癌细胞的细胞周期改变和凋亡影响,及其放疗增敏的作用及机制。方法:体外培养非小细胞肺癌细胞株A-549,分单纯培养细胞组、单纯照射组、单纯吉西他滨组及吉西他滨联合放疗组(联合放疗组);单纯照射组采用源皮距(SSD)为100 cm,剂量2 Gy,6 MV光子线照射;吉西他滨组采用MTT法选择对细胞生长抑制率≤10%的药物浓度(IC10)即为GEM的最佳实验浓度;联合放疗组采用最佳实验浓度的GEM加上述同等条件的照射剂量和方法;流式细胞仪分析上述各组细胞的细胞周期和凋亡率。结果:经MTT法检测显示,GEM在0.020-0.030μmol/L之间时为最佳实验浓度。流式细胞仪分析各处理组细胞的细胞周期和凋亡率结果表明,各处理组之间细胞在S期时的比例有显著差异(P<0.05),G2/M、S期比值变化最为明显;细胞凋亡率亦有统计学差异(P<0.05);单纯采用GEM浓度为0.02,0.03μmol/L时没有明显差别(P>0.05)。结论:吉西他滨可以具有放射增敏和协同作用,其机制可能与吉西他滨能改变A-549细胞生长周期并诱导其凋亡有关。

Objective： To study the growth inhibition and radiosensitivity effect of Gemcitabine on nonsmall cell lung cancer （NSCLC） cells. Methods： The NSCLC cell line A-549 were cultured in vitro and randomized into control, radiation alone, Gemcitabine alone and combination treatment group. The radiation group were radiated by SSD（100 cm/2Gy, 6MeV）. The IC10 was determined by MTT method in Gemcitabine group, and the combination group were treated with the optimal dose of Gemcitabine and radiation. Then the flow cytometry were applied to detect the cell cycle and apoptosis ratio of non-small cell lung cancer cell line A-549 in each group. Results： MTT method suggested that the optimal dose of Gemcitabine were 0. 020-0. 030 μmol/L. It was confirmed by FACS that there were significant differences among each treatment group on S stage cell ratio （P〈0.05）. Apoptosis ratio was different between each group （P〈0.05）, except that between 0.02 μmol/L and 0.03 μmol/L（P〉0.05） group. Conclusion. Radiosensitivity and synergistic effect can be enhanced by Gemcitabine. The mechanism may be related with Gemcitabineinduced apoptosis and modified cell cycle in non-small cell lung cancer cell A-549.