黏蛋白1基因转染DC对乳腺癌细胞MCF-7裸鼠移植瘤的免疫抑制作用  

Immuno-inhibitory effect of DC transfected with MUC1 gene on xenograft tumor of the breast carcinoma MCF7 cell in nude mouse

作　　者：尹良伟[1] 马海英[2] 张利[3] 王贺双[3] 刘宇[1] 于环[1] 祝艳华[1] 伍建林[4] 

机构地区：[1]大连医科大学附属大连市中心医院肿瘤内三科,辽宁大连116033 [2]大连医科大学组织胚胎学教研室,辽宁大连116044 [3]大连医科大学附属大连市中心医院中心实验室,辽宁大连116033 [4]大连大学附属中山医院医学影像教研室,辽宁大连116033

出　　处：《中国肿瘤生物治疗杂志》2017年第7期756-761,共6页Chinese Journal of Cancer Biotherapy

基　　金：大连市卫计委科研课题资助项目(No.2012-0407L)~~

摘　　要：目的:探讨黏蛋白1(mucin 1,MUC1)基因转染DC对人乳腺癌MCF-7细胞裸鼠移植瘤的抑制作用。方法:体外诱导培养健康成人DC,应用脂质体转染法将pc DNA3.1-MUC1转染DC,ELISA法检测转染后DC分泌细胞因子IL-12和TNF-α的能力,LDH释放法检测基因转染后DC诱导特异性CTL对乳腺癌MCF-7细胞的杀伤活性。应用MUC1基因转染DC、空质粒转染DC、及生理盐水皮下注射治疗人乳腺癌MCF-7细胞裸鼠移植瘤,观测其对肿瘤生长的抑制作用。结果:转染pc DNA3.1-MUC1的DC分泌IL-12、TNF-α的能力较转染空质粒DC明显增强[IL-12:(202.52±29.61)vs(10.83±1.02)pg/ml;TNF-α:(349.07±79.42)vs(9.26±1.52)pg/ml,均P<0.01];转染pc DNA3.1-MUC1的DC诱导产生特异性CTL,对人乳腺癌MCF-7细胞具有更明显的杀伤活性,效靶比为10∶1、5∶1和2.5∶1时的杀伤率分别达到56.2%、38.9%和25.8%,显著高于对照组CTL(均P<0.01)。MUC1基因转染DC对乳腺癌MCF-7裸鼠移植瘤生长抑制作用明显强于空质粒转染DC组(P<0.05)。结论:MUC1基因转染DC可以诱导特异性CTL,对乳腺癌MCF-7细胞具有更强的抗肿瘤免疫效应。Objective： To explore inhibitory effect of dentritic cell （DC） transfected with mucin 1 （MUC1） gene on xenograft tumor of human breast carcinoma MCF7 cell in nude mouse. Methods： DC of healthy adults were in-duced-cultured in vitro. Plasmid with human pcDNA3.1-MUC1 gene were transfected into the DC by a lipofection assay. ELISA assay was used to detect secretion ability of cytokines IL-12 and TNF-α by the transfected DC. LDH release assay was used to exam killing activity of specific cytotoxic T lymphocytes （CTL） induced by the transfect-ed DC to the breast carcinoma MCF7 cell. The xenograft tumors of human breast carcinoma MCF7 cell in nude mice were treated by the DC transfected with MUC1 gene, the DC transfected with empty plasmid and normal sa-line in subcutaneous injection, and growth inhibition of the xenograft tumors in nude mice were observed. Results：Secretion abilities of IL-12 and TNF-α by the DC transfected with pcDNA3.1-MUC1 gene were obviously more en-hanced than those by the DC transfected with empty plasmid （ IL-12：[202.52±29.61] vs [10.83±1.02] pg/ml; TNF-α：[349.07±79.42] vs [9.26±1.52] pg/ml, all P〈0.01）. Killing activity of the specific CTL induced by the DC transfect-ed with pcDNA3.1-MUC1 genewas more obvious than that by the CTL of the control group, and the killing rates at effector/targetor ratio of 10：1, 5：1 and 2.5：1 were 56.2%, 38.9% and 25.8% respectively （all P〈0.01）. Inhibitory ef-fect of the DC transfected with MUC1 gene on the xenograft tumors of breast carcinoma MCF7 cell in nude mice was significantly stronger than that of the DC transfected with empty plasmid （P〈0.05）. Conclusion： The DC trans-fected with MUC1 gene might induce specific CTL, which might have stronger anti-tumor immuno effect on the breast carcinoma MCF7 cell.

关 键 词：MUC1基因 树突状细胞 基因转染 乳腺癌 免疫效应 

分 类 号：R737.9[医药卫生—肿瘤] R730.51[医药卫生—临床医学]