一定浓度下三氧化二砷对T细胞淋巴瘤Hut-78细胞株增殖的影响

Effect of arsenic trioxide on proliferation of T cell lymphoma cell line Hut-78

背景:近年来有将三氧化二砷试用于T细胞肿瘤的有效报道,但未见其治疗机制的相关研究。目的:检测三氧化二砷对人皮肤T细胞淋巴瘤Hut-78细胞的抑制增殖、诱导凋亡及细胞周期的影响。方法:分别采用MTT、PI单标记流式细胞术和TUNEL法检测2,5,10μmol/L的三氧化二砷干预24,48,72h,对人皮肤T细胞淋巴瘤Hut-78细胞株抑制增殖、诱导凋亡和细胞周期的影响,及其凋亡相关基因bcl-2及血管内皮细胞生长因子基因表达的变化。结果与结论:在一定的浓度范围内,三氧化二砷对Hut-78细胞存在增殖抑制作用,其增殖抑制作用在一定程度上可能与下调血管内皮细胞生长因子基因的表达有关,同时还存在一定的细胞毒作用;三氧化二砷可诱导Hut-78细胞发生凋亡,凋亡机制主要发生在G2～M期,其凋亡作用可能与下调bcl-2基因表达有关。三氧化二砷对Hut-78细胞的增殖抑制及诱导凋亡作用呈时间剂量依赖性。

BACKGROUND：In recent years,although some effective therapies of arsenic trioxide for T cell lymphoma have been reported,this mechanism is yet unknown.OBJECTIVE：To investigate the effect of arsenic trioxide on inhibiting proliferation,inducing apoptosis and cell cycle of T cell lymphoma cell line Hut-78 cells.METHODS：The inhibitory effect of arsenic trioxide（2,5,10 μmol/L for 24,48,72 hours） on proliferation and its inducing apoptosis effect,influence on cell cycle of Hut-78 cell line were detected by MTT,flow cytometry with PI staining and terminal deoxynucleotidy transferase-mediated dUTP nick end-labeling（TUNEL） assay.The transcription level changes of bcl-2 gene and vascular endothelial growth factor（VEGF） gene was measured by RT-PCR.RESULTS AND CONCLUSION：In the concentration range of 2-10 μm/L of arsenic trioxide,with the increasing of concentration and extending of action time,the growth inhibition of Hut-78 cells was gradually increased.The apoptosis of Hut-78 mainly occurred at G2-M phase.The effect of arsenic trioxide to induce Hut-78 apoptosis could be related to down-regulation of bcl-2 gene.Arsenic trioxide has an influence on inhibiting proliferation and inducing apoptosis of Hut-78 in a time-and dose-depended manner.