阿托伐他汀对人NK细胞杀伤结肠癌细胞的影响及其机制研究  

Effect and mechanism of atorvastatin on cytotoxicity of human NK cells to colon cancer cells

作　　者：姬会春 刘军权[2] 周燏[2] 李昳[2] 陈复兴[2] 费素娟[3] 

机构地区：[1]宿迁市第一人民医院,宿迁223800 [2]中国人民解放军97医院,徐州221000 [3]徐州医学院附属医院消化科,徐州221000

出　　处：《中国免疫学杂志》2017年第2期178-185,共8页Chinese Journal of Immunology

基　　金：南京军区医学科技创新课题经费资助项目(13MA039)资助

摘　　要：目的:探讨阿托伐他汀对人NK细胞杀伤结肠癌细胞的影响及其机制。方法:不同浓度的阿托伐他汀作用于3株结肠癌细胞(HCT-116、SW-480、Caco-2),CCK-8法测定阿托伐他汀对结肠癌细胞生长抑制率的影响。SCGM培养基体外扩增人NK细胞,自动生化分析仪测定NK细胞对3株结肠癌细胞的杀伤活性;流式细胞仪检测结肠癌细胞MICA/B的表达率。结果:(1)NK细胞的培养:培养前CD3-CD56+的NK细胞占外周血单个核细胞的比例为4.5%,培养10 d时NK细胞的比例增至93.1%。(2)阿托伐他汀对3株结肠癌细胞生长抑制率的影响:阿托伐他汀作用48 h后,在浓度5~40μmol/L的4个实验组中,HCT-116细胞的生长抑制率较对照组升高(P<0.05)。作用96 h后,在1.25~40μmol/L的所有浓度组(6个)中,HCT-116细胞的生长抑制率均显著高于对照组(P<0.05)。另外,HCT-116细胞的生长抑制率随着阿托伐他汀浓度的升高而逐渐上升,相关分析显示,阿托伐他汀的浓度与HCT-116细胞的生长抑制率呈正相关(r[48 h]=0.13,r[96 h]=0.22,P<0.05)。(3)NK细胞经阿托伐他汀作用96 h后,除浓度为20μmol/L和40μmol/L时抑制率高于对照组,其他各组对NK细胞生长无明显影响。(4)阿托伐他汀对NK细胞杀伤结肠癌细胞活性的影响:NK细胞对HCT-116细胞的杀伤活性在阿托伐他汀浓度2.5~10μmol/L组均显著高于对照组,对SW-480的杀伤活性在5~20μmol/L组较对照组明显升高,对Caco-2的杀伤活性在2.5~20μmol/L组显著高于对照组(P<0.05),其中同一浓度时对HCT-116细胞杀伤作用最强。(5)阿托伐他汀对结肠癌细胞MICA/B表达的影响:在阿托伐他汀浓度2.5μmol/L及5μmol/L组,HCT-116细胞MICA/B的表达率与对照组比较显著升高(P<0.05),在10μmol/L及20μmol/L组,SW-480细胞MICA/B表达率显著高于对照组(P<0.05),在2.5~40μmol/L组,Caco-2细胞MICA/B的表达率均较对照组显著升高(P<0.05)。结论:(1)阿托伐他汀能够呈剂量依赖性抑制结肠癌细胞HCT-116�Objective： To explore the mechanism of the cytotoxicity of human NK cells induced by atorvastatin to colon cancer cell lines. Methods： After colon cancer cells（ HCT-116,SW-480,Caco-2） were cultured with different concentrations of atorvastatin,CCK-8 assay was used to assess the effect of atorvastatin on growth of colon cancer cells. The amplification of human NK cells was induced by SCGM medium in vitro. Automatic biochemical analyzer was applied to test the cytotoxicity of NK cells to colon cancer cells which cultured with different concentration of atorvastatin. FCM was used to detect the expression rate of MICA / B on the cells. Results：（ 1） The cultivation of NK cells： The proportion of NK cells attained to 93. 1% from 4. 5% after cultured for 10 days.（ 2） The effects of atorvastatin on the growth of the colon cancer cells： After cultured with atorvastatin,the inhibition rate of HCT-116 cells was higher than that in control when the density of atorvastatin increased from 5 μmol / L to 40 μmol / L after 48 h and from 1. 25 μmol / L to40 μmol / L after 96 h（ P 0. 05）. Correlation analysis showed that the concentration of atorvastatin and the growth inhibition rate of HCT-116 cells were positively correlated（ r[48 h]= 0. 13,r[96 h]= 0. 22,P〈0. 05）.（ 3） The cytotoxicity of NK cells to colon cancer cells effected after atorvastatin： In different atorvastatin concentrations groups,the cytotoxicity of NK cells to three colon cancer cell lines was all higher than that in control（ P 〈0. 05）. The atorvastatin concentration was from 2. 5 μmol / L to 10 μmol / L for HCT-116 cells,from 5 μmol / L to 20 μmol / L for SW-480 cells,and from 2. 5 μmol / L to 20 μmol / L for Caco-2 cells. Among the three cell lines,the cytotoxicity of NK cells to HCT116 was the highest in the same concentration.（ 4） NK cells by atorvastatin cutting statins 96 h,the concentration of 20 mmol / L and 40 mmol / L inhibition rate was higher than that of control group,more than other groups on

关 键 词：阿托伐他汀 结肠癌细胞 NK细胞 MICA/B 

分 类 号：R735.3[医药卫生—肿瘤]