小鼠皮下人乳腺癌移植瘤模型的建立及应用

发布时间：2018-03-09 10:50

本文选题：人乳腺癌　切入点：异种移植肿瘤动物模型　出处：《吉林大学》2009年硕士论文　论文类型：学位论文

【摘要】： 人类肿瘤动物模型是抗肿瘤药物药效学研究的重要手段。尽管裸鼠和SCID鼠是异种移植性动物模型中最常用的实验动物,可用于抗肿瘤药物的筛选与开发,但不适合肿瘤疫苗的研究。肿瘤疫苗主要通过增强机体的主动免疫达到治疗肿瘤目的。因此,对于肿瘤疫苗研究,必须建立免疫功能正常的肿瘤模型。MUC1是粘蛋白家族成员,是肿瘤疫苗研究的理想靶分子。MUC1-MBP是本研究组通过基因工程技术制备的融合蛋白,能特异性诱导小鼠细胞免疫应答和体液免疫应答,抑制小鼠Lewis肺癌的生长,但其对人乳腺癌的作用还不清楚。本研究利用ICR小鼠建立人类乳腺癌皮下移植瘤模型,利用该模型初步探讨MUC1-MBP抗人乳腺癌作用。研究采用ICR小鼠,先经X射线和免疫抑制剂处理后使其暂时处于免疫抑制状态,然后皮下注入人类乳腺癌细胞;通过解剖观察、HE染色和免疫组织化学染色对人乳腺癌组织进行鉴定;筛选5 Gy X射线照射,每只ICR鼠皮下注射乳腺癌MCF-7细胞3 X 10~6,FTY-720灌胃4-6天为最佳实验条件,成功建立小鼠皮下人乳腺癌移植瘤动物模型。采用Amylose Resin亲和层析获得纯化的MUC1-MBP及MBP蛋白。利用已经建立的乳腺癌动物模型,观察MUC1-MBP和MBP抗乳腺癌作用。结果显示MUC1-MBP和MBP蛋白免疫对人乳腺癌的预防和治疗均具有明显的作用,MUC1-MBP比MBP抗肿瘤作用显著。本研究建立的肿瘤模型方法简便,成瘤率高,死亡率低,可用于观察肿瘤疫苗的抗肿瘤活性,为肿瘤免疫治疗研究提供新的研究工具。
[Abstract]:Animal models of human tumor is an important means to study efficacy of antitumor drugs. Although nude mice and SCID mice are the most commonly used experimental animal xenograft animal model, can be used for screening and development of anti-tumor drugs, but not suitable for the study of tumor vaccine. The tumor vaccine mainly through enhanced active immune to cancer therapy objective. Therefore, for the study of tumor vaccine, must establish the tumor model.MUC1 normal immune function is a member of the mucin family, is the ideal target molecule.MUC1-MBP of tumor vaccine is the study of fusion protein by genetic engineering technology to prepare the mice cellular immune response and humoral immune responses induced by the specific inhibition of Lewis lung cancer in mice the growth of human breast cancer, but its role is still unclear. This study used ICR mice model of human breast cancer xenograft model, using the model at the beginning The effect of MUC1-MBP on human breast cancer is discussed step by step.
Study on the ICR mice by X ray and immunosuppressive treatment make it temporarily areimmunosuppressed, then subcutaneous injection of human breast cancer cells; through anatomical observation, HE staining and immunohistochemical staining were used to identify breast cancer screening; 5 Gy X rays, each ICR rat subcutaneous injection of breast cancer MCF-7 3 X 10~6 FTY-720 cells, by gavage for 4-6 days for the best experimental conditions, successfully established animal model of mice breast cancer. Using Amylose Resin MUC1-MBP and MBP protein was purified by affinity chromatography. The animal model of breast cancer has been established, MUC1-MBP and MBP to observe the effect of anti breast cancer. The results showed that the prevention and treatment of MUC1-MBP and MBP protein in human breast cancer have obvious effect, MUC1-MBP than the antitumor effect of MBP is significant.
The tumor model established in this study is simple, with high tumorigenicity and low mortality. It can be used to observe the anti-tumor activity of tumor vaccine and provide a new research tool for the research of tumor immunotherapy.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R-332;R737.9

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