CIK体外抗癌活性分子机制的探讨  

Mechanism of anti-cancer activities of cytokine induced killer cells in vitro

作　　者：李芳秋[1] 张蕾[1] 刘群[1] 黄海嵘[2] 李德闵[2] 

机构地区：[1]南京军区南京总医院解放军临床检验医学研究所临床中心实验科,江苏南京210002 [2]南京军区南京总医院解放军临床检验医学研究所临床中心心胸外科,江苏南京210002

出　　处：《中华肿瘤防治杂志》2009年第13期994-997,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：南京市科技发展计划项目(200401070-5)

摘　　要：目的:分析细胞因子诱导的杀伤细胞(cytokine induced killer cell,CIK)抗肿瘤活性增强的分子机制。方法:从健康人志愿者和恶性肿瘤患者PBMC培养获得CIK细胞,用LDH释放法分别对PBMC和CIK进行体外杀伤肿瘤细胞的活性测定,用流式细胞术分析PBMC和CIK细胞群中颗粒溶素(granulysin,GNLY)和穿孔素(perforin,PFN)的表达。结果:在效靶比为5∶1时,健康人和肿瘤患者PBMC对肿瘤细胞K562的裂解率分别为6.33%和1.29%,两组CIK细胞对肿瘤细胞K562的裂解率分别为14.7%和14.16%,PB-MC与CIK对细胞的裂解率显著提高,P<0.01;GNLY阳性表达细胞百分比由4.43%和1.95%上升到19.15%和17.52%,P<0.01。但PFN细胞却由21.91%和14.69%降低到4.96%和3.7%,P<0.05。结论:肿瘤患者PBMC抗肿瘤活性下降可能与该细胞中GN-LY和PFN表达减少有关;CIK细胞杀伤肿瘤活性的提高可能与GNLY的表达增加相关;PFN表达下降可能是维持CIK细胞在体外大量增殖的调节因素。OBJECTIVE： To study the molecular mechanism of the increase in anti cancer activity of cytokine induced killer （CIK） cells. METHODS： CIK cells were generated from peripheral mononuclear cells （PBMC） of healthy and cancer patient volunteers. Anticancer activity of PBMC and CIK cells were measured in vitro by LDH release assay and the amount of granulysin （GNLY） and perforin （PFN） expressed in two kinds of cell populations determined by flow cytometry. RESULTS： At an effector target cell ratio of 5 ： 1, PBMCs from healthy and cancer patient volunteers destroyed 6.33% and 1.29% of K562 cells respectively; CIK cells from the two groups de stroyed 14.7% and 14.16% of K562 cells respectively. The percents of GNLY cells in PBMCs increased from 4.43% and 1.95% to 19. 15% and 17.52% in CIKs（P〈0.01）, however, the percents of PFN cells declined from 21.91% and 14.69% to 4.96% and 3.7% （P〈0.05）, respectively. CONCLUSIONS： The impairment of the expressions of GNLY and PFN in PBMCs ceils accompanies the decline of anti-cancer activity of cancer patients. Higher cytotoxic efficiency of CIK cells against its target is related to the increasing expressions of GNLY. The decline of PFN may be needed for keeping CIK cell proliferation in large number.

关 键 词：肿瘤/免疫学 细胞因子类 免疫疗法 过继 杀伤细胞 淋巴因子激活 

分 类 号：R730.5[医药卫生—肿瘤]