重组鼠Muc1-MBP融合蛋白疫苗体内抗肿瘤作用  

Anti-tumor effect induced by recombinant mouse Muc1-MBP fusion protein in vivo

作　　者：方芳[1] 宋献美[1] 马吉春[1] 张庆勇[1] 窦蕊[1] 陈文博[1] 柳忠辉[1] 台桂香[1] 

机构地区：[1]吉林大学白求恩医学院免疫学教研室,吉林长春130021

出　　处：《第四军医大学学报》2009年第22期2541-2544,共4页Journal of the Fourth Military Medical University

基　　金：吉林省科技发展计划项目(20080931)

摘　　要：目的:研究重组鼠Muc1-MBP蛋白的体内抗肿瘤作用.方法:采用皮下注射法将不同剂量Muc1-MBP蛋白免疫小鼠,2wk/次,共免疫3次.在第3次免疫后4d,给予C57BL/6小鼠尾静脉注射LLC1细胞,或给予5GyX射线照射的ICR小鼠背部皮下注射MCF-7细胞.注射3wk后剥离并测量肿瘤大小;肿瘤组织行常规HE染色.免疫组织化学染色分析肿瘤周围浸润的淋巴细胞亚群.结果:LLC1细胞尾静脉接种后21d,肺肿瘤结节对照组,Muc1-MBP0.15g/L组小鼠分别为54和39个(100%),Muc1-MBP0.3g/L组小鼠共计17个(60%),提示Muc1-MBP0.3g/L组可显著抑制肺癌的生长(P<0.05),Muc1-MBP0.15g/L组作用较弱.皮下接种MCF-7细胞后21d,对照组,Muc1-MBP0.15g/L组小鼠100%(6/6)可见乳腺癌瘤体形成,平均体积分别为(142.8±70.2)和(96.1±53.4)mm3,Muc1-MBP0.3g/L组瘤体形成66.7%(4/6),平均体积为(54.5±46.7)mm3.表明Muc1-MBP0.3g/L组免疫后可显著抑制人乳腺癌移植瘤生长(P<0.05),Muc1-MBP0.15g/L组作用较弱.免疫组化结果显示Muc1-MBP免疫组肿瘤周围有大量CD4+和CD8+T的细胞浸润到肿瘤周围.结论:Muc1-MBP诱导免疫能够明显抑制LLC1,MCF-7细胞的生长,为临床应用研究奠定了基础.AIM：To study the anti-tumor effect of recombinant Muc1-MBP protein in vivo.METHODS：Mice were immunized subcutaneously with different dose of Muc1-MBP protein 3 times at 2-weekly intervals.C57 BL /6 mice were challenged with LLC1 cells by tail vein or ICR mice irradiated with X-ray injected MCF-7 cells at back 4 d after the third immunization.The tumor was striped and measured 3 weeks later.Histological analysis of tumor tissuewas carried out with HE staining.Tumor infiltrating lymphocytessubsets were detected by immunohistochemistry.RESULTS：After 21 d of LLC1 cell challenge,there was only 60% forming lung tumor nodules and total number 17 in high dose Muc1-MBP group,while there was 100% forming lung tumor nodules in low dose Muc1-MBP group and control group and total number of tumor nodules was 39 and 54 in low dose and control group respectively.The results showed that tumor growth using high dose MUC1-MBP was obviously suppressed（P〈0.05）,without statistically difference in low dose group.After 21 d of MCF-7 cell challenge,the tumor formation rate in control group and low dose Muc1-MBP group was 100%（6/6）,while 66.7%（4/6）mice formed tumors in high dose Muc1-MBP group.The volumes of tumor in control group,high dose group and low dose group were respectively（142.8±70.2）,（54.5±46.7）and（96.14±53.37）mm^3.There are significant tumor inhibitory effect in high dose Muc1-MBP（P〈0.05）,but not in low dose Muc1-MBP,compared with that control group.The result showed that tumor growth using high dose Muc1-MBP was obviously suppressed（P〈0.05）,but low dose group were not significantly changed.A number of CD4＋ and CD8＋T cells were infiltrated into cancerous tissue in Muc1-MBP group.CONCLUSION：Muc1-MBP protein vaccine can significantly suppress the growth of LLC1 lung cancer and MCF-7 breast cancer,and provide a basis for clinical research.

关 键 词：MUC1 Muc1-MBP融合蛋白 异种同源蛋白 肿瘤疫苗 

分 类 号：R730.5[医药卫生—肿瘤]