磁热化疗对人胶质母细胞瘤U251及其uPA系统的抑制作用

目的 研究磁热化疗联合作用对人胶质母细胞瘤U251的抑制作用及其机制分析.方法 采用溶剂挥发法制备纳米Fe3O4粒子及抗肿瘤药物多西紫杉醇共混的复合膜,植入U251荷瘤裸鼠皮下模型肿瘤,通过体外交变磁场加热,观察裸鼠肿瘤体积及生存期,通过免疫组化方法观察检测肿瘤组织的尿激酶型纤溶酶原激活物(urokinase plasminogen activation,uPA),尿激酶型纤溶酶原激活物受体(urokinase plasminogen activation receptor,uPAR)及纤溶酶原激活物抑制剂1(plasminogenactivator inhibitor 1,PAI-1)的表达.结果 对照组肿瘤终末体积为3 683.16mm3,中位生存期13d；热疗组1 156.12mm3,中位生存期30d；化疗组2 749.943mm3,中位生存期18d；热化疗组71.882 25mm3,中位生存期41d.与对照组相比,热化疗组uPA,uPAR及PAI-1表达均有明显下调(P＜0.05).结论 热化疗联合应用可通过下调U251的uPA系统表达而抑制胶质瘤的侵袭和复发.

Inhibitory effect of magnetic thermochemotherapy on human glioblastoma U251 and its urokinase plasminogen activation system

Objective To study the inhibitory effect of magnetic thermochemotherapy on human glioblastoma U251 and its mechanism.Methods Magnetic nanocomposite polymeric film,was fabricated with solvent cast method and coated with nanosized Fe3O4 and docetaxel mixture.The composited film was implanted into U251 xenografts and heated by alternating magnetic field.Survival time of nude mice and volume of U251 xenografts were observed.Expressions of urokinase plasminogen activation（uPA）,urokinase plasminogen activation receptor（uPAR） and plasminogen activator inhibitor-1（1PAI-1） in U251 tissue were detected with the immunohistochemical method.Results The final U251 volume in and survival time of nude mice were 3 683.16mm3 and 13 days respectively in control group,1 156.12mm3 and 30 days respectively in thermotherapy group,2 749.943mm3 and 18 days respectively in chemotherapy group,71.882 25mm3 and 41 days respectively in thermochemotherapy group.The expression levels of uPA,uPAR and PAI-1 were significantly lower in thermochemotherapy group than in control group（P〈0.05）.Conclusion Thermochemotherapy can significantly inhibit the invasion and relapse of U251 by down-regulating the expression of its uPA system.