Anti-uPAR单克隆抗体顺铂对胶质瘤增殖和uPAR蛋白表达的影响

The Study of the Effects of Anti-uPAR,Cisplatin on the Growth of Human Gliomas and the Expression of uPAR Protein

目的研究Anti-uPAR单克隆抗体、顺铂对人脑胶质瘤细胞U251皮下瘤增殖影响以及尿激酶型纤溶酶原激活因子受体(uPAR)在U251皮下瘤的表达特征,评估其在胶质瘤恶性生长方式中的作用。方法以人脑胶质瘤细胞株U251为材料,制作裸鼠皮下胶质瘤模型。应用Anti-uPAR单克隆抗体、抗肿瘤药物顺铂干预肿瘤生长进程,使用免疫组化技术观察uPAR在肿瘤细胞的表达以及抗肿瘤效果。结果Anti-uPAR单克隆抗体、抗肿瘤药物都成功地抑制了肿瘤的生长,顺铂只能够降低U251移植瘤的增殖,而不能象Anti-uPAR单克隆抗体一样抑制肿瘤的生长并能使之缩小。顺铂抑制了uPAR蛋白在U251肿瘤细胞上的表达。结论uPAR与内源性uPA的结合是胶质瘤增殖及其生存的关键所在,针对uPA/uPAR为靶点的治疗方案可能为胶质瘤的治疗开辟一条新的研究思路。

Objective To study the patterns of the expression of urokinase- type plasminogen activator receptor in human glioma of subcutaneous model. The growth of the glioma infected by the Anti- uPAR, cisplatin was primary studied. Methods Subcutaneous glioma model was made using established human glioma cell line U251, and nude mouse. The growing rate and mode was observed. Immunohistochemistry was performed to study the growth of the glioma interrupted by using Anti- uPAR monoclonal antibody or cisplatin. Results The intensity of the immunoreaction correlated with growing rate of glioma. Cisplatin only can decelerated the growing of glioma, but not reduced volume of subcutaneous glioma like Anti- uPAR monoclonal antibody had done. Conclusion uPA bounding with its receptor uPAR is the key that glioma grow and survive. Treatment targeting uPA/uPAR could be a useful therapeutic strategy for glioma.