三氧化二砷对人脐静脉内皮细胞中蛋白激酶C活性和白细胞介素-15分泌、表达的影响及其临床意义  

Effect of arsenic trioxide on PKC activity and expression and secretion of interleukin 15 in human um-bilic vascular endothelial cells and its clinical significance

作　　者：吴柱国[1] 赵家明[2] 孟琼[1] 张毅[2] 

机构地区：[1]广东医学院附属医院儿科,广东湛江524001 [2]广东医学院附属医院中心实验室

出　　处：《中华实验外科杂志》2004年第9期1126-1128,共3页Chinese Journal of Experimental Surgery

摘　　要：目的 通过研究三氧化二砷(As2O3)对人脐静脉内皮细胞(HUVEC)中蛋白激酶C(PKC)活性和白细胞介素(IL)-15表达和分泌的影响,探讨内皮细胞在As2O3抑制白血病或肿瘤中的作用。方法用不同浓度的As2O3作用于培养的HUVEC细胞,测定其生长情况、胞膜和胞浆PKC活性以及对IL-15基因表达和分泌的影响。结果0.25 μmol／L^50 μmol／L的.As2O3均抑制HUVEC细胞的增殖(P<0.01),随着药物浓度或作用时间的增加,细胞逐渐死亡。在As2O3作用细胞4 h测定胞浆和胞膜的PKC活性,两者在不同浓度作用下活性水平均得到提升(P<0.01),但胞膜的活性上升幅度更大。在As2O3的测定浓度范围内,PKC的活性水平与As2O3的浓度呈正相关。1、5、16 μmol／L的As2O3导致IL-15基因表达和分泌水平的增加(P<0.01),并呈浓度依赖性关系。结论As2O3可能是通过激活内皮细胞的PKC活性,促进IL-15或其他细胞因子的分泌,来抑制白血病或肿瘤发展的。Objective To explore the effect of arsenic trioxide (As2O3) on the protein kinase C (PKC) activity and the expression and secretion of interleukin 15 (IL-15) in human umbilic vascular en-dothelial cells (HUVECs) and to discuss the role of endothelial cells in the inhibition of tumors and leukemias by arsenic trioxide. Methods The cultured HUVECs were treated with different concentrations of arsenic trioxide, and the PKC activity and IL-15 mRNA expression and protein secretion were assayed. Results Arsenic trioxide from 0.25 μmol/L to 50 μmol/L could inhibit the growth of HUVEVs (P<0.001),and long-time and high-concentration treatment led to cell death.This treatment also could up-regulate the PKC activity and enhance the expression and secretion of interleukin 15 (IL-15) significantly in a concentration-dependent manner (P<0. 001) . Compared with the cytosolic PKC activity, the membrane-bound PKC activity experienced a more rapid and higher increase. Conclusion The inhibition of tumors and leukemias by arsenic trioxide is partly contributed to the secretion of IL-15 and others cy-tokines via PKC activation.

关 键 词：AS2O3 PKC 表达 分泌 HUVEC 人脐静脉内皮细胞 三氧化二砷 蛋白激酶C 水平 增殖 

分 类 号：R965[医药卫生—药理学]