IL-12诱导急性单核细胞白血病细胞分化及凋亡的机制研究  

The Mechanism of IL-12 for the Differentiation and Apoptosis of Acute Mononuclear Leukemia Cells

作　　者：吴碧涛 马婷婷[1] 林艳[1] 熊海玉[1] 王秦[1] 成凤[1] 李紫薇[1] 涂植光[1] 

机构地区：[1]重庆医科大学检验医学院临床检验诊断学教育部重点试验室,重庆400016

出　　处：《中国细胞生物学学报》2015年第5期677-682,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81172016)资助的课题~~

摘　　要：白细胞介素-12(interleukin-12,IL-12)具有明显的抗肿瘤作用,但其作用机制较复杂。前期形态学和功能的研究发现,IL-12可诱导单核细胞白血病细胞分化。该研究从巨噬细胞表面分化标志、细胞增殖能力、周期以及凋亡四个方面探讨了IL-12诱导急性单核细胞白血病细胞分化和凋亡的相关作用机理。结果发现,以人源性重组IL-12 p70处理的THP-1细胞,巨噬细胞表面标志CD68和CD11b的表达量明显增加并呈时间依赖性,CD68+和CD11b+阳性细胞数也显著增多;IL-12诱导分化过程中伴有THP-1细胞生长缓慢、G1期或G1/S期细胞周期阻滞现象;IL-12处理后的THP-1细胞凋亡率也明显增加,以早期凋亡细胞为主,并伴有抗凋亡蛋白Bcl-2表达下调及促凋亡蛋白Fas表达增加。上述实验结果提示,IL-12对于急性单核细胞白血病可通过诱导肿瘤细胞向成熟巨噬细胞分化,抑制细胞增殖以及增加细胞凋亡来发挥抗肿瘤作用。As we all know, interleukin-12 （IL-12） plays a critical role in anti-tumor responses Our previous morphological and functional study has revealed that over-expression of IL-12 would induce monocytic leukemia cell differentiation. In this study, we examined the differentiation markers, changes of cell proliferation, cell cycle and apoptosis in THP-1 cells after IL-12 treatment to investigate its likely mechanism for the differentiation and apoptosis of acute mononuclear leukemia cells. It was found that the macrophage surface marker CD68 and CD I i b mRNA and protein expression increased in a time-dependent manner, and CD68＋ and CDllb＋ positive cells significantly increased. Furthermore, IL-12-induced THP-1 cell differentiation was accompanied by the G1 or GI/S phase growth arrest with G1 phase ceils accumulation and S phase ceils reduction. Cell apoptosis rate increased significantly, especially the early apoptosis cells; anti-apoptosis protein Bcl-2 was down-expressed, and pro-apoptosis protein Fas was up-regulated. These findings have revealed that IL-12 is likely to play a role of anti-tumor on acute mononuclear leukemia through inducing monocytic tumor cellsdifferentiation to mature macrophages, suppressing tumor cells malignant proliferation and increasing tumor cells apoptosis.

关 键 词：白细胞介素-12 急性单核细胞白血病 分化治疗 

分 类 号：R733.7[医药卫生—肿瘤]