姜黄素对CIK细胞杀伤胃癌细胞株SGC-7901作用的影响及其机制的研究

The curcumin-induced CIK cell cytotoxicity to gastric cancer cell line SGC-7901 and its mechanism

目的探讨姜黄素对细胞因子诱导的杀伤细胞(CIK细胞)杀伤胃癌细胞株SGC-7901作用的影响及其机制。方法10名健康者外周血单个核细胞(PBMC)在体外经多种细胞因子诱导为CIK细胞;收集培养第5天的CIK细胞,给予不同浓度的姜黄素诱导,37℃、5%CO2条件下继续培养72 h,LDH法检测CIK细胞对SGC-7901细胞的杀伤活性;FACS法检测CIK细胞表型CD3+CD8+、CD3+CD56+含量及穿孔素、颗粒酶B水平。结果①姜黄素诱导后,CIK细胞杀伤胃癌SGC-7901的活性明显提高,在10μmol/L时杀伤活性显著高于对照组(P<0.05)。②姜黄素诱导后,CIK细胞内穿孔素和颗粒酶B的水平明显提高(P<0.05)。③姜黄素能够显著增加CIK细胞的CD3+CD56+表达(P<0.05),降低其CD3+CD8+表达(P<0.05)。结论姜黄素能提高CIK细胞对胃癌细胞株SGC-7901的杀伤活性,其机制可能与其增加CIK细胞穿孔素和颗粒酶含量以及增加CD3+CD56+表达有关。

Objective To investigate the effect and the underlying mechanism of the curcumin-induced cytotoxicity of CIK cells to gastric cancer cell line SGC-7901 in vitro.Methods The peripheral blood mononuclear cells（PBMC） from 10 healthy volunteers were induced in vitro with different cytokines and transferred into CIK cells.On the fifth day,the CIK cells were collected and were induced with the addition of curcumin at different concentrations,followed by 72 hours of culture under the condition of 37℃ and 5% CO2.The antitumor cytotoxicity of CIK cells to cell line SGC-7901 was determined by LDH assay.The content of phenotypes CD3＋CD8＋ and CD3＋CD56＋ of CIK cells,the levels of perforin and granzyme B were analyzed by a fluorescence activated cell sorter（FACS）.Results ①The anti-tumor cytotoxicity of CIK cells exposed to curcumin on SGC-7901 was markedly elevated and the cytotoxicity reached 62.32%±1.28% at a concentration of 10 μmol/L curcumin,with significant differences in contrast with the control group（37.45%±1.12%,P〈0.05）.②The level of perforin and granzyme B of CIK cells induced by curcumin remarkably increased（P0.05）.③Curcumin could evidently upregulate the expression of CD3＋CD56＋ of CIK cells（P〈0.05） and downregulate the expression of CD3＋CD8＋ of CIK cells,compared with the control group（P〈0.05）.Conclusion Curcumin can enhanced the CIK cell cytotoxicity to gastric cancer SGC-7901 and this mechanism is involved in the increase of perforin and granzyme B content as well as the upregulation of CD3＋CD56＋ expression.