阿托伐他汀对人NK细胞杀伤HCT-116细胞的影响及其机制研究

The effect and mechanism of Atorvastatin on the cytotoxicity of human NK cells to HCT-116 cells

目的探讨阿托伐他汀对人自然杀伤细胞（natural killer,NK）杀伤HCT-116细胞的影响及其机制。方法 CCK-8法测定不同浓度的阿托伐他汀对HCT-116细胞生长抑制率的影响。自动生化分析仪测NK细胞对HCT-116细胞的杀伤活性;流式细胞仪（FCM）检测HCT-116细胞MICA/B的表达率。结果不同浓度的阿托伐他汀作用于HCT-116细胞48 h后在浓度为5~40μmol/L及作用96 h后在浓度为1.25~40μmol/L时,对HCT-116细胞的生长抑制率与对照组相比差异有统计学意义（P〈0.05）。阿托伐他汀浓度相同时,HCT-116细胞的生长抑制率在48 h组与96 h组相比,除5μmol/L浓度组外差异均有统计学意义（P〈0.05）。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）。NK细胞对HCT-116细胞的杀伤活性在阿托伐他汀浓度为2.5~10μmol/L各组中均显著高于对照组（P〈0.05）。2.5μmol/L浓度组及5μmol/L浓度组,HCT-116细胞MICA/B的表达率与对照组比较显著升高（P〈0.05）。结论阿托伐他汀呈剂量依赖性抑制HCT-116细胞的生长,且延长作用时间可以增强阿托伐他汀对HCT-116细胞生长的抑制作用;还能够增强NK细胞对HCT-116杀伤活性;以及上调HCT-116细胞MICA/B的表达率,提高其免疫原性。

Objective To investigate the mechanism of the cytotoxicity of NK cell induced by Atorvastatin to HCT-116 cells. Methods The effect of different concentrations of Atorvastatin on the growth of HCT-116 cells was measured by CCK-8. Automatic biochemical analyzer was applied to test the cytotoxicity of NK cells to HCT-116 cells. Flow cytometry（ FCM） was used to detect the expression rate of MICA / B in the cells. Results Atorvastatin could inhibit the growth of HCT-116 cells,the inhitbition rates of HCT-116 were higher than those in the control group in different concentrations of Atorvastatin treatment 48 hours and 96 hours. Statistical analysis showed that the inhibition rates of HCT-116 had significant difference compared with the control group（ P〈0. 05） when Atorvastatin was 5-40 μmol / L after48 hours and 1. 25-40 μmol / L after 96 hours. 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）. The cytotoxicity of NK cells to HCT-116 cells was higher than the control group when Atorvastatin was 2. 5-10 μmol / L（ P〈0. 05）. The expression of MICA / B on HCT-116 cells was higher than the control group（ P〈0. 05） in the concentration of 2. 5 μmol / L and 5 μmol / L. Conclusion Atorvastatin could inhibit the growth of HCT-116 cells in a dose-dependent manner; and it could enhance the cytotoxic activity of the NK cells to HCT-116 cells; it also could promote the expression of MICA / B on HCT-116 cells,and improve the immunogenicity of HCT-116 cells.