培美曲塞对外周T细胞淋巴瘤细胞Jurkat及Hut-78生长抑制作用的实验研究

Effect of Pemetrexed on the Growth of Human T-cell Lymphoma Cell Jurkat and Hut-78

目的观察不同浓度培美曲塞作用于外周T细胞淋巴瘤细胞Jurkat及Hut-78细胞后的不同时间的外周T细胞淋巴瘤的细胞生长抑制情况,并探讨其可能的细胞学机制.方法1.不同浓度（终浓度分别为0.01μg/mL、0.1μg/mL、1μg/mL、10μg/mL、100μg/mL）培美曲塞分别作用于外周T细胞淋巴瘤细胞Jurkat及Hut-78细胞后24h、48h,用CCK-8测定细胞杀伤.2.不同浓度（终浓度分别为0.01μg/mL、0.1μg/mL、1μg/mL、10μg/mL、100μg/mL）培美曲塞分别作用于外周T细胞淋巴瘤细胞jurkat及hut-78细胞48h,流式细胞术测定药物作用后细胞株细胞周期分布的变化.结果不同浓度的培美曲塞对Jurkat及Hut-78细胞均具有显著杀伤作用,随时间延长,细胞抑制更明显.培美曲塞对外周T细胞淋巴瘤细胞株jurkat及Hut-78具有明显的细胞周期阻滞作用,将细胞周期阻断在S期.结论培美曲塞具有抑制人T细胞淋巴瘤细胞生长的作用,细胞周期阻滞作用可能为其相关的细胞学机制.提示培美曲塞有望成为人T细胞淋巴瘤治疗的新的途径.

Objective To investigate the growth inhibition effects and the possible mechanism of pemetrexed on human T-cell lymphoma cell lines Jurkat and Hut-78 in vitro.Methods The Jurkat and Hut-78 cells were treated with different concentrations of pemetrexed.At 24h,48h after treatment,cell viability was evaluated by CCK-8 and after the treatment with different concentrations of pemetrexed,the change of cell cycles were detected by flow cytometry.Results The growth of Jurkat and Hut-78 cells was inhibited by pemetrexed in a dose- and time-dependent manner.In addition,the flow cytometry profiles revealed that the treatment with different concentrations of pemetrexed（48h） led to shift from 26.07% up to 27.91%,32.89%,36.81%,41.29% and 51.69% in percentage of cell line Jurkat with a s-like DNA content.And the flow cytometry profiles also revealed that the treatment led another shift from 63.31% down to 57.85%,55.74%,56.80%,46.66% and 37.38% in percentage of cell line Jurkat with a G0/G1-like DNA content.With same treatment,the percentage of cell line Hut-78 with a G0/G1-like DNA content reduced from 69.33% to 68.56%,67.48%,59.52%,51.43% and 45.58%;the percentage of cell line Hut-78 with a s-like DNA content increased from 14.93% up to 18.70%,22.01%,28.37%,35.66% and 39.29%.Conclusion Pemetrexed could inhibit the proliferation of human T-cell lymphoma cell Jurkat and Hut-78.The cell cycle arresting may play an important role of anti-tumor effect of pemetrexed.Our study suggests a potential role of pemetrexed in the clinical treatment of T-cell lymphoma.