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目的:研究人粘蛋白MUC1基因DNA疫苗诱导小鼠体内免疫应答及对乳腺肿瘤的特异性抑制作用。方法:采用股四头肌注射法接种PcDNA3.1(+)-MUC1质粒,通过ELISA法检测小鼠血清MUC1抗体、脾细胞产生IL-2和IFN-γ的量及血清中TNF水平,通过乳酸脱氢酶释放法测定CTL对MCF-7细胞的杀伤活性。结果:经PcDNA3.1(+)-MUC1免疫小鼠后脾细胞分泌IL-2、IFN-γ及血清TNF水平较对照组明显增高,差异有统计学意义;在效靶比为100∶1、50∶1、25∶1、12.5∶1时,MUC1基因疫苗免疫组小鼠CTL对人乳腺癌细胞系MCF-7杀伤率分别为63.8%、51.2%、43.5%、22.5%,较空载体PcDNA3.1(+)组小鼠和灭菌生理盐水组小鼠均明显升高,差异有统计学意义(P<0.05)。结论:MUC1基因DNA疫苗能够激活小鼠Th1细胞,诱导小鼠产生抗MUCl特异性抗体,诱导产生杀伤高表达MUC1基因的乳腺癌细胞的CTL,为MUC1基因疫苗用于乳腺肿瘤生物治疗提供了一定的实验依据。
AIM: To investigate the immunosuppression induced by human mucin MUC1 DNA vaccine in mice and its specific inhibitory effect on breast tumors. Methods: PcDNA3.1 (+) - MUC1 plasmid was inoculated into the quadriceps femoris and the levels of IL-2 and IFN-γ in serum were detected by ELISA. The levels of TNF- Dehydrogenase release assay CTL cytotoxicity to MCF-7 cells. Results: The levels of IL - 2, IFN - γ and TNF secreted by spleen cells of mice immunized with PcDNA3.1 (+) - MUC1 were significantly higher than those of the control group (P <0.05) 50: 1, 25: 1, 12.5: 1, the killing rate of CTL on MCF-7 cells in mice immunized with MUC1 gene vaccine were 63.8%, 51.2%, 43.5% and 22.5% .1 (+) mice and sterilized saline groups were significantly increased, the difference was statistically significant (P <0.05). CONCLUSION: MUC1 DNA vaccine can activate mouse Th1 cells, induce MUC1-specific antibodies in mice, induce CTLs that kill MUC1-overexpressing breast cancer cells, and provide some evidence for MUC1 gene vaccine to be used in breast tumor biotherapy Experimental basis.