【摘要】 目的建立小鼠皮下人乳腺癌移植瘤模型,探讨MUC1-MBP蛋白疫苗的抗人乳腺癌作用。方法首先通过筛选最佳条件建立小鼠皮下人乳腺癌移植瘤动物模型,HE染色和免疫组化鉴定。利用已经建立的乳腺癌动物模型,通过肿瘤预防实验和治疗实验,观察MUC1-MBP抗人乳腺癌作用。结果通过5 Gy X射线照射,皮下注射MCF-7人乳腺癌细胞3×10~6个/只,FTY720灌胃4～6 d,成功建立小鼠皮下人乳腺癌移植瘤动物模型。在预防乳腺癌生长实验中,PBS对照组、MBP组和MUC1-MBP组小鼠成瘤率分别为100%、83%和67%,肿瘤平均体积分别为(91.9±56.3)mm~3、(22.3±21.5)mm~3和(17.2±18.0)mm~3。与对照组相比,MUC1-MBP组显著减小(P<0.001),MBP组明显减小(P<0.05),提示MUC1-MBP能明显预防乳腺癌生长,MBP对乳腺癌生长也有一定的预防作用。在治疗乳腺癌生长实验中,PBS对照组、MBP组和MUC1-MBP组小鼠肿瘤生长抑制率分别为0、17%和17%,肿瘤平均体积分别为:(101.7±73.6)mm~3、(56.9±56.7)mm~3和(32.6±32.3)mm~3,与对照组相比,MUC1-MBP组明显减小(P<0.05),差异显著,提示MUC1-MBP对乳腺癌具有治疗作用。MBP组无显著差异(P>0.05),无统计学意义,提示MUC1-MBP对乳腺癌具有治疗作用。肿瘤组织HE染色结果发现,MUC1-MBP和MBP免疫组小鼠肿瘤组织周围及癌细胞间淋巴细胞浸润较PBS组明显增多。结论成功建立ICR小鼠皮下人乳腺癌移植瘤模型,该模型为肿瘤疫苗活性研究提供良好的研究工具。利用该模型发现MUC1-MBP免疫明显抑制小鼠皮下人乳腺癌的生长,MBP免疫也具有一定的抗乳腺癌生长作用,其能明显增强MUC1的免疫原性。更多还原

【Abstract】 We established a subcutaneous human breast cancer transplantation model in mice for studying the anti-breast cancer effect of MUC1-MBP vaccine.Firstly,Subcutaneous transplantation tumor model of human breast cancer in mice was established by irradiating with 5Gy X-ray,inoculating s.c.into each ICR mice with 3×10~6 MCF-7 cells,and administrating with lavage of FTY720 for 4～6 days.Then hematoxylin and eosin(HE) stain and immunohistochemistry were used to identify the model.Anticancer effect of MUC1-MBP was observed by cancer-prevention and cancer-treatment experiments using established mouse model.In prevention experiment, incidence of breast cancer in mice of MUC1-MBP,MBP,and PBS groups were 67%,83%,and 100%,respectively,while their mean tumor volumes were(17.2±18.0) mm~3,(22.3±21.5) mm~3 and(91.9±56.3) mm~3,respectively.Compared with PBS group, mean sizes of tumor in MUC1-MBP(P<0.001) and MBP group(P<0.05) were significantly smaller,which suggested that both MUC1-MBP and MBP have preventive effects on human breast cancer and MUC1-MBP anticancer activity is more significant,compared with MBP.In treatment experiments,inhibitory rate of tumor growth in the MUC1-MBP,MBP,and PBS groups were 17%,17%, and 0,while their mean tumor volumes were(32.6±32.3) mm~3,(56.9±56.7) mm~3,and(101.7±73.6) mm~3,respectively.Compared with PBS group,the volumes of MUC1-MBP(P<0.05) and MBP group(P>0.05) were smaller,which suggested that both MUC1-MBP and MBP could inhibit human breast cancer and MUC1-MBP anticancer activity is more significant,compared with MBP.In this study,we successfully established subcutaneous transplantation mouse model of human breast cancer,which provide a useful tool for cancer vaccine immunity activity research.Furthermore our data suggest that MUC1-MBP could break up immuniology tolerance and obviously inhibit breast cancer growth;MBP also had the anticancer function and could significantly enhance the immunity activity of MUC1.更多还原