转染MIP-1α和B7-1基因增强小鼠的抗淋巴瘤效应  

Inhibitory effect of MIP-1α and B7-1 gene transfection on mouse lymphoma

作　　者：刘伟[1] 余英豪[1] 

机构地区：[1]南京军区福州总医院病理科,福州福建350025

出　　处：《中国比较医学杂志》2013年第6期38-43,I0005-I0007,共9页Chinese Journal of Comparative Medicine

基　　金：南京军区医学科学技术研究"十一五"计划课题(编号:07Z034);福建省自然科学基金(编号:2010J01221)资助

摘　　要：目的观察转染趋化因子MIP-1α和共刺激分子B7-1基因增强小鼠抗淋巴瘤的效应。方法将MIP-1α和B7-1基因慢病毒重组载体转染小鼠EL-4淋巴瘤细胞,应用RT-PCR检测MIP-1α和B7-1基因mRNA表达,Western blot法检测MIP-1α和B7-1蛋白表达;转基因EL-4细胞注入小鼠右腋皮下,观察成瘤情况;灭活的转基因EL-4细胞注入成瘤小鼠体内,观察其增强小鼠抗淋巴瘤效应。结果 RT-PCR检测发现EL-4/MIP-1α+B7-1细胞内有MIP-1α及B7-1mRNA表达,Western blot显示MIP-1α及B7-1蛋白表达;MIP-1α组、B7-1组较对照组成瘤时间延长,成瘤率降低,肿瘤平均体积较小,而联合组成瘤性消失;MIP-1α和B7-1治疗组的肿瘤平均体积、重量及肿瘤器官转移率明显小于对照组(P<0.05),而联合组的肿瘤平均体积及重量明显小于MIP-1α和B7-1组(P<0.05),而且联合组小鼠平均生存期,均较单基因组、对照组明显延长(P<0.05)。结论转染MIP-1α和B7-1基因能够明显增强小鼠机体抗淋巴瘤效应,明显延长荷瘤小鼠的平均生存期,为淋巴瘤的基因治疗提供了新的思路。Objective To study the antitumor effect of MIP-lα and B7-1 gene transfection on mouse lymphoma. Methods Mouse lymphoma EL-4 cells were transfected by lentivirus-mediated mouse MIP-lc~ and B7-1 gene vectors. MIP-lα and B7-1 mRNA were identified by RT-PCR, and MIP-lα and B7-1 proteins were determined by Western blot. The transfected EL-4 cells were injected into the right axilla in mice to induce tumor growth. The transfected EL-4 cells were inactivated and injected into tumor-bearing mice to observe their antitumor effect. Results RT-PCR assay showed expressions of MIP-lα and B7-1 mRNA in the EL-4/MIP-1α ＋ B7-1 cells, and Western blot revealed expression of MIP-1α and B7-1 proteins. The tumor formation was retarded, tumor formation rate was decreased, and the tumor was smaller in the MIP-lα group and B7-1 group than that in the control group, and no tumor was formed in the MIP-lα ＋ B7-1 group. The mean tumor volume, weight and organ metastasis rate of the MIP-1α and B7-1 groups were significantly lower than that of the control group （ P 〈 0.05 ） , while the mean tumor volume and weight of the MIP-1 ce ＋ B7-1 group were significantly lower than that of the MIP-lα group and B7-1 group （P 〈0.05）. In addition, the mean survival time of the MIP-lα ＋ B7- 1 group was significantly longer than that in the single groups and the control group （ P 〈 0. 05 ）. Conclusions Lentivirus- mediated mouse MIP-lα and B7-1 gene transfection can effectively enhance the anti-lymphoma effect on tumor-bearing mice, and can significantly prolong the mean survival time of tumor-bearing mice. It may provide a new idea for genetherapy of lymphoma in future.

关 键 词：慢病毒载体 EL_4细胞 MIP-1α基因 B7—1基因 淋巴瘤 

分 类 号：R33[医药卫生—人体生理学]