寡脱氧核糖核苷酸联合CA125共致敏树突状细胞对裸鼠人卵巢癌移植瘤生长抑制作用  

Immunosuppressive action of dendritic cells sensitized by oligodeoxynucleotides and CA125 on human OVCAR3 ovarian carcinoma xenografts in nude mice

作　　者：叶明珠[1] 李娜[1] 黄秀敏[1] 王达颖[1] 商晶[1] 

机构地区：[1]厦门大学附属中山医院妇产科,福建省厦门市361004

出　　处：《中华医学杂志》2014年第15期1193-1195,共3页National Medical Journal of China

基　　金：福建省自然科学基金（2010D016）

摘　　要：目的探讨含未甲基化“胞嘧啶-磷酸二酯键-鸟嘌呤（CpG）基序”的寡脱氧核糖核苷酸（CpGODN）联合肿瘤表面抗原CA125共致敏树突状细胞（DC）对裸鼠人卵巢癌移植瘤生长的免疫抑制作用。方法自人外周血分离培养DC，流式细胞术鉴定DC表型特征；应用CpGODN2006联合CA125体外冲击致敏DC，并与T淋巴细胞共培养获得细胞毒性T淋巴细胞（CTL）。建立人OVCAR3卵巢癌荷瘤裸鼠模型，CTL经皮下注射免疫荷瘤裸鼠，绘制移植瘤生长曲线，通过计算抑瘤率、细胞凋亡率评估其对裸鼠人OVCAR3卵巢癌移植瘤的免疫抑制作用。结果分离培养DC低水平表达CD83、CD86，符合未成熟DC表型特征；联合致敏DC与T淋巴细胞共培养后获得CTL，经皮下免疫治疗，肿瘤出现延迟生长，抑瘤率达50．71％，抑瘤效果优于单纯CpGODN致敏组和单纯CA125致敏组，差异有统计学意义（P〈0．05）。联合致敏组和单纯CpGODN致敏组肿瘤细胞凋亡率分别为（29．6±3．0）％和（21．8±2．7）％，均显著高于未致敏组和CA125致敏组（P〈0．05）。结论CpGODN联合CA125共致敏DC体外活化的CTL可有效抑制卵巢癌移植瘤生长，促进瘤细胞凋亡。Objective To explore the immunosuppressive action of dendritic cells （DC） sensitized by oligodeoxynucleotides containing ＂ un-methylated cytimidine-phosphodiester bond-guanylic acid＂ motif （ CpG ODN） and CA125 on human ovarian carcinoma xenografts in nude mice. Methods Human peripheral blood-derived dendritic cells were isolated and identified by flow cytometry. The DC sensitized by CpG ODN and CA125 were then co-cultured with T cells and finally cytotoxic T lymphocytes （CTL） were induced. Nude mice bearing OVCAR3 transplanted tumor were immunized with induced CTL by subcutaneous injection and tumor growth and cell apoptosis observed. Results Premature DC had a low expression of CD83 and CD86. In vivo, delayed growth of OVCAR3 xenografts was observed after immunotherapy with CTL induced by DC pulsed by CpG ODN and CA125. The inhibition rate of tumor was 50.71% and it was better than CpG ODN-pulsed and CA125-pulsed groups （ P 〈 0.05 ）. Cell apoptotic rate was （ 29. 6 ± 3.0 ） % in CpG ODN ＋ CA125-pulsed group versus （21.8 ± 2. 7 ） % in CpG ODN-pulsed group. And both were more than those of unpulsed and CA125-pulsed groups （ P 〈 0. 05 ）. Conclusion CTL induced by DC sensitized by CpG ODN and CA125 can inhibit the growth of ovarian carcinoma xenografts and promote tumor cell apoptosis.

关 键 词：寡脱氧核糖核苷酸 卵巢癌 裸鼠 异种移植 免疫治疗 

分 类 号：R737.31[医药卫生—肿瘤]