目的: 探讨细胞因子诱导杀伤细胞(cytokine induced killer cell,CIK)对裸鼠胃癌移植瘤的靶向抑制作用。方法:将人胃癌细胞SGC 7901注射到裸鼠腹股沟皮下建立胃癌移植瘤裸鼠模型,荷瘤裸鼠随机分为CIK细胞组与成纤维细胞组,分别注射荧光染料SP DiI标记的CIK细胞与成纤维细胞(HFL I)于裸鼠种植瘤对侧腹股沟皮下, 观察其在荷胃癌裸鼠体内各种组织中的分布情况;同时观察CIK治疗后肿瘤的体积大小并计算抑瘤率,病理观察肿瘤的坏死面积。结果: SP DiI标记的CIK细胞注射后10 d主要浓集在荷瘤裸鼠的肿瘤组织,注射局部、肝脏、脾脏和肺脏组织中无CIK细胞或分布极少(P<001);标记的成纤维细胞没有出现在肿瘤组织、肝脏、脾脏和肺脏组织,主要集中于注射局部。CIK细胞治疗后裸鼠的移植瘤体积显著小于对照组(P<0.05),其抑瘤率为29.82%;移植瘤组织坏死面积评分显著高于对照组(P<0.01)。结论: CIK细胞对裸鼠胃癌移植瘤有良好的靶向性和杀伤性。
objective: To study the in vivo anti tumor effect of exosomes (Exo) combined with bacillus Calmette Guérin vaccine(BCG). Methods:Exo was isolated and purified from culture supernatant of E.G7 OVA tumor cells by density gradient centrifugation. Protein components of Exo were detected by Western blotting. Exo, BCG, Exo combined with BCG (Exo+BCG) or PBS were pre injected into mice before injection of E.G7 OVA cells, and the anti tumor effects were observed in each group. Mouse model bearing E.G7 OVA cells was established to examine the immuno therapy effects of Exo with or without BCG. Cytotoxity of spleen CTL was measured by LDH in different groups. Results: Exo derived from E.G7 OVA cells contained HSP60, OVA, HSC70 and CD63 as detected by Western blotting. Tumor free rate at 90 d was significantly higher in Exo+BCG vaccinated mice than those in Exo or BCG vaccinated mice as measured by immuno protective assay (60% vs 20% or 0%,P<0.01). Immuno therapy assay showed that tumor inhibitory effect in Exo+BCG group was significantly higher than those in Exo or BCG groups (P<0.01). CTL results showed that CTL of Exo+BCG vaccinated mice had significantly enhanced ability to specifically kill target E.G7 OVA cells compared with those of Exo and BCG groups (P<0.01). Conclusion: BCG as an immuno adjuvant can significantly enhance the anti tumor effect of exosomes in vivo.