ErbB2高表达的人乳腺癌原位移植瘤裸鼠模型的建立

Establishment of nude mice xenograft model of human breast cancer with ErbB2 overexpression

目的采用人乳腺癌细胞株BT-474建立稳定高表达ErbB2的人乳腺癌裸鼠移植瘤模型,选择合适的模型制作方法。方法实验前1d在36只裸鼠颈部皮下埋植0.5mg17β雌二醇缓释片,并随机分为3组:原位组将5×106个BT-474细胞接种于裸鼠左侧第二乳房垫内,胁部皮下组将同样数量的BT-474细胞接种于裸鼠左侧胁部皮下,腋窝组则接种于裸鼠左侧腋窝内;观察3组裸鼠荷瘤情况及移植瘤病理组织学特点,并采用免疫组化方法动态监测移植瘤的ErbB2表达情况。结果 3组裸鼠的荷瘤率均为100%,都保持了原发肿瘤高表达ErbB2的特点;和两组对照相比,原位组肿瘤形状、生长速度及细胞增殖与血管生成等生物学特征一致性更强;此外,原位组的肿瘤对治疗药物处理也有良好反应。结论 BT-474细胞接种于乳房垫内比胁部皮下及腋窝建立的裸鼠移植瘤模型更适于进行抗ErbB2抗体等药物的药理学研究。

Aim To select a good inoculation method of BT-474 cell to establish a stable animal model of ErbB2-overexpressing human breast cancer in nude mice.Methods 36 nude mice received implants of 0.5 mg 17β-estradiol 60 d-release estrogen pellets and were randomly divided into three groups.The next day 5×10 6 BT-474 cells were injected into left second mammary fat pad of every mouse in the orthotopic group,left flank in the flank group or left axilla in the axilla group,respectively.The tumor growth and histopathological features of BT-474 xenografts in the three groups were observed and compared,and ErbB2 expression on tumor cell surface was evaluated by immunohistochemistry. Results The tumor-bearing rate of the nude mice in the three groups were all 100%,and the breast cancer xenografts all remained stable ErbB2 overexpression.However,the xenografts in the orthotopic group had less variance in tumor size,form and biological characteristics such as potent cell proliferation and angiogenesis compared with the control.Moreover,the orthotopic xenografts had a good response to the drugs.Conclusion The human breast cancer model established by orthotopic inoculation of BT-474 cell is more suitable than that in the flank or axilla for the pharmacological research of ErbB2-targeted therapeutics.