白细胞介素-24 delE5对人类白血病细胞系K562的抑制作用  

Effects of IL-24 delE5 on human leukemia cell line K562

作　　者：王琳[1] 马小彤[1] 董成亚[1] 张芳[1] 段永娟[1] 杨宾霞[1] 林永敏[1] 

机构地区：[1]中国医学科学院 北京协和医学院血液学研究所 血液病医院 实验血液学国家重点实验室,天津300020

出　　处：《白血病．淋巴瘤》2010年第3期129-132,共4页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金（30872983,30672364）

摘　　要：目的 探索白细胞介素（IL）-24 delE5对人类白血病细胞系K562的抑制作用.方法 用TPA诱导白血病细胞系U937和HL-60向单核-巨噬细胞分化后,检测mda-7/IL-24及其选择性剪接体IL-24delE5的表达.构建IL-24 delE5真核表达载体,稳定转染K562细胞.通过MTT法、集落形成实验、流式细胞术、Annexin-V/PI检测及动物实验,观察IL-24 delE5对K562细胞增殖、集落形成、细胞周期、凋亡及体内致瘤性的影响;同时与mda-7/IL-24进行比较.结果 在TPA诱导分化的U937和HL-60细胞中发现IL-24 delE5的表达.稳定转染IL-24 delE5的K562增殖及集落形成明显下降,与空载体相比,G0/G1期细胞比例由（24.46±3.99）%增至（42.69±3.04）%,细胞周期阻滞于G0/G1期,体内实验证实K562细胞移植瘤生长明显被抑制.与mda-7/IL-24相比,上述各实验结果差异均无统计学意义.结论 IL-24 delE5与mda-7/IL-24一样对人类白血病细胞系K562具有明显的体内外抑制作用,该作用可能与IL-24 delE5所引起细胞周期G0/G1期阻滞有关.Objective To investigate the antitumor activity of IL-24 delE5 in human leukemia cell line K562. Methods The expression of mda-7/IL-24 and its splice variant induced by TPA in leukemic cell lines, U937 and HL-60, was evaluated. The effects of IL-24 delE5 in K562 on cell proliferation, colony-forming ability, cell cycle, apoptosis, and tumor growth in vivo by using MTr assay, colony forming assay, flow cytometry, Annexin-V/PI and tumor xenograft models in nude mice were assessed. Meantime, the effects of IL-24 delE-5 and mda-7/IL-2A were compared. Results The expression of IL-24 dciE5 was detected in differentiated U937 and HL-60 cells. Transfection with IL-24 delE5 significantly reduced tumor cell viability, inhibited colony formation. Comparing with the control, G0/G1 stage add from （24.46±3.99） % to （42.69±3.04） %, caused cell cycle arrest in G0/G1 stage and significantly inhibited the growth of K562 transplantation tumor. No significant differences in the aforementioned antileukemia characteristics between IL-24 delE5 and mda-7/IL-24 was found. Conclusion Similar with mda-7/IL-24, IL-24 delE5 can efficiently inhibit the proliferation of K562 in vitro and in vivo, probably through induction of G0/G1 cell cycle arrest.

关 键 词：黑素瘤分化相关基因 剪接体 基因治疗 K562细胞 细胞周期 

分 类 号：R733.7[医药卫生—肿瘤]