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.

辽宁省科技发展计划重点项目（No.20082250085）