DC-CIK共培养细胞联合索拉菲尼对肝癌细胞体内外的杀伤效应  

In vitro and in vivo cytotoxicity effects of co-cultured DC-CIK cells combined with sorafenib against hepatocellular carcinoma

作　　者：李卿[1] 王新利[1] 王杨[1] 隋承光[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤研究所,辽宁沈阳110001

出　　处：《中国肿瘤生物治疗杂志》2010年第1期46-50,共5页Chinese Journal of Cancer Biotherapy

基　　金：辽宁省科技发展计划重点项目(No.2008225008-5)~~

摘　　要：目的:观察DC、CIK共培养细胞(DC-CIK)联合索拉菲尼(sorafenib)对肝癌细胞BEL-7402的体内外杀伤效应。方法:取健康人外周血单个核细胞,加入不同细胞因子促进DC及CIK细胞成熟并混合共培养。CCK8试剂盒检测DC-CIK共培养细胞联合索拉菲尼对BEL-7402细胞的体外杀伤效应,Annexin V-FITC试剂盒检测两者联合对肝癌细胞凋亡率的影响。用肝癌细胞BEL-7402建立裸鼠皮下移植瘤模型,分为生理盐水对照组、索拉菲尼组、DC-CIK组、DC-CIK+索拉菲尼组,观察它们对裸鼠移植瘤生长的抑制作用。结果:联合组对肝癌细胞的杀伤率及诱导凋亡率均明显高于各单独治疗组,联合组杀伤率高达(75.24±1.91)%,是DC-CIK组的1.8倍,是索拉菲尼单药组的2.1倍(P<0.01);联合组诱导肝癌细胞凋亡率达(78.32±2.54)%,与单独治疗组相比差异有统计学意义(P<0.05)。体内实验表明,DC-CIK+索拉菲尼组可明显抑制裸鼠BEL-7402移植瘤的生长,抑制率为(83.37±0.16)%,与单独治疗组相比差异有显著统计学意义(P<0.01)。结论:DC-CIK共培养细胞联合索拉菲尼在体内、外可显著抑制肝癌细胞的生长,分子靶向治疗联合细胞免疫治疗可能成为肝癌综合治疗的方法之一。Objective：To investigate the in vitro and in vivo inhibitory effects of DC （dendritic cell）-CIK （cytokine-induced killer cell） co-cultured cells combined with sorafenib against hepatocellular carcinoma cell line BEL-7402.Methods：DC and CIK cells were generated in vitro by stimulating human peripheral blood mononuclear cells with different cytokines,and then they were co-cultured.The cytotoxicity of DC-CIK co-cultured cells （DC-CIK） combined with sorafenib against BEL-7402 cells was determined by CCK8 kit.The apoptosis of BEL-7402 cells was measured by Annexin V-FITC Kit.BEL-7402-implanted tumor model was established by subcutaneous injection in nude mouse.Tumor-bearing mice were divided into normal saline control group,sorafenib group,DC-CIK group and DC-CIK＋sorafenib group.The inhibitory effects were observed in different groups.Results：The cytotoxicity rate of BEL-7402 cells in DC-CIK＋sorafenib group was significantly higher than those in the other two groups,with cytotoxicity rate in DC-CIK＋sorafenib group being （75.24±1.91）%,which was 1.8 times that in DC-CIK group and 2.1 times that in sorafenib group （P〈0.01）.The apoptosis rate of BEL-7402 cells in DC-CIK＋sorafenib group was significantly higher than those in the sorafenib and DC-CIK groups,with the apoptosis rate in DC-CIK＋sorafenib group being （78.32±2.54）% （P〈0.05）.The volume of tumor in the combination group was significantly smaller than those in the other groups （P〈0.05）.In vivo results showed that DC-CIK＋sorafenib treatment significantly inhibited the growth of BEL-7402-implanted tumors,and the inhibitory rate was （83.37 ±0.16）%,which was significantly higher than those of the other groups （P〈0.01）.Conclusion：DC-CIK co-cultured cells combined with sorafenib can inhibit the growth of hepatocellular carcinoma cell line BEL-7402 in vitro and in vivo.Molecular targeting therapy combined with immunotherapy may be a new way for the comprehensive treatment of hepatocellular carcinoma.

关 键 词：肝肿瘤 树突状细胞 细胞因子活化的杀伤细胞 索拉菲尼 

分 类 号：R735.7[医药卫生—肿瘤] R730.54[医药卫生—临床医学]