NDV联合负载胃癌细胞抗原DC-CIK对胃癌细胞的杀伤效果及机制

Synergistic anti-gastric cancer effect and mechanism of Newcasatle Diease virus in combination with gastric cancer antigen loaded dendritic cells

目的探讨新城疫病毒(NDV)联合负载胃癌细胞抗原(Ag)的树突状细胞(DC)及细胞因子诱导的杀伤细胞(CIK)对胃癌细胞的杀伤效果及机制。方法用人外周血单个核细胞诱导培养DC及CIK,体外培养人胃癌细胞SGC-7901,反复冻融法制备胃癌细胞Ag悬液冲击致敏DC,CIK与负载胃癌细胞Ag的DC共培养。建立胃癌裸鼠模型,将其随机分为四组各6只。PBS组瘤内注射PBS 100μl/只;NDV组瘤内注射NDV0.25 ml/只;Ag-DC-CIK组瘤内注射负载抗原的DC诱导的CIK细胞0.2 ml/只;NDV+Ag-DC-CIK组先瘤内注射NDV0.25 ml/只,1 d后再注射负载抗原的DC诱导的CIK细胞0.2 ml/只;各组均隔日注射1次,共3次。14 d后测量肿瘤体积,计算抑瘤率。观察肿瘤坏死情况并评分。结果NDV+Ag-DC-CIK组肿瘤平均体积小于NDV组和Ag-DC-CIK组,抑瘤率、肿瘤坏死面积评分高于NDV组和Ag-DC-CIK组;P均<0.05。结论NDV和负载胃癌细胞Ag的DC-CIK能协同杀伤胃癌细胞,杀伤效果强于二者单用效果;其机制为NDV可增加胃癌细胞的抗原性,为CIK细胞提供更多靶点。

Objective To investigate the anti-gastric cancer effect and mechanism of eytokine induced killer cells pulsed with gastric cancer antigen loaded dendritic cells （Ag-DC-CIK） in combination with Neweasafle Diease virus （NDV）. Methods CIK cells and DC cells were induced and cultured by mononuclear cells from peripheral blood of healthy adult. Human gastric cancer cells SGC-7901 were eultured in vitro and the antigen suspension of gastric cancer cells prepared by repetitive freeze thaw method was used to allergize DC cells. Model of gastric cancer were established in 24 mice and divided into PBS group, NDV group , Ag-DC-CIK group and NDV ＋ Ag-DC-CIK group on average. Then PBS, NDV ,Ag-DC-CIK ,NDV ＋ Ag-DC-CIK were injected into tumors of which respectively. The volume of tumor was meas- ured to calculate the tumor inhibitory rate, the necrosis area scores were noted after HE stain. Results Compared with the NDV group or Ag-DC-CIK group ,the average volume of tumor in NDV ＋ Ag-DC-CIK group reduced,while the tumor inhibi- tory rare and the score of tumor necrosis area increased. Conclusion CIK pulsed with gastric cancer antigen loaded DC combined with NDV have a synergistic effect to kill gastric cancer ceils. The mechanism is that NDV can enhance the antigenieity of gastric cancer cells, so as to afford more targes for the CIK cells.