MSC联合磁流体热疗治疗肺癌的实验研究  

Mesenchymal Stem Cells Labeled with Fluorescent Magnetic Nanoparticles for Hyperthermia of Lung Cancer

作　　者：胡润磊[1] 江洪[1] 薛庆明[1] 丁艺晖 魏东山[1] 马胜林[1] Hu Rualei;Jiang Hong;Xue Qingming(Department of Cardiothoracic Surgery,Hangzhou First People's Hospital ,Zhejiang 310006,China)

机构地区：[1]杭州市第一人民医院心胸外科,310006

出　　处：《医学研究杂志》2018年第11期107-110,120,共5页Journal of Medical Research

基　　金：浙江省科技计划项目(2015C37083);浙江省医药卫生科技计划项目(2014KYB187);杭州市医药卫生重点项目(2012Z002)

摘　　要：目的探讨磁流体热疗与MSC对肺癌裸鼠移植瘤的治疗作用。方法体外制作FMNP-MSC;建立肺癌A549裸鼠皮下移植瘤模型,等肿瘤直径长至约4mm时,将FMNP-MSC通过小鼠尾静脉注射到体内。注射后1周,在交变磁场下热疗,每周1次,时间30min,连续4周,光纤测温检测肿瘤温度的变化,每周测量瘤体的长径和短径变化。治疗4周后,球取血观察白细胞变化,离断法处死小鼠,取出肿瘤组织,称取瘤重;光镜观察各组肿瘤组织病理学变化,Western blot法检测FMNP-MSC热疗后凋亡蛋白(Bax、caspase-3)、抗凋亡蛋白(Bcl-2)的表达。结果 MSC可以将FMNP携带至肿瘤区域,小鼠的白细胞无明显变化,在交变磁场的作用下可以升温至53℃,荷瘤小鼠肿瘤体积和重量增长受到明显抑制。病理观察可见肿瘤细胞大片凋亡和坏死样改变。Western blot法检测证实Bax蛋白在两个治疗组明显表达。结论 MSC可以将FMNP携带到小鼠皮下移植肿瘤区域,在交变磁场作用下升温至有效温度,小鼠肿瘤的生长受到明显抑制,肿瘤组织呈凋亡和坏死样改变,可能是通过增加Bax的表达来实现的。Objective To study therapeutic effects of fluorescent magnetic nanoparticles labeled mesenchymal stem cells (FMNP-MSC)for hyperthermia induced by an alternating magnetic field on lung cancer A549 in nude mice.Methods The fluorescent magnetic nanoparticles (FMNP)was prepared and characterized,and then were used to label mouse mesenchymal stem cells(MSCs)in vitro.The FMNPs -labeled MSCs were injected via tail vein into nude mice bearing non -small cell lung cancer A549 cells.The subcutaneous lung cancer tissues in the nude mice models were subsequently treated in external alternating magnetic field once a week for four weeks.Temperature of tumor was detected by optical fiber.Four weeks after treatment,blood samples were collected from the eyes of the mice,and the tumor were collected after euthanizing the animals.Pathology change of tumor tissue was detected by light microscope,cell apoptosis proteins (Bax,caspase-3)and anti -apoptotie protein (Bcl-2)were detected by Western blot.Results In vivo experiments confirmed that MSC FMNP can be carried to the tumor area.Temperature of tumor can heat up to 53℃ under alternating magnetic field. FNMP -MSC thermal therapy group mice tumor volume and weight growth was significantly inhibited,FMNP -MSC group of mice with tumor volume growth is restrained.The weight was not significantly inhibited.Apoptosis and necrosis change of tumor tissue could be detected by light microscope.Western blot confirmed that Bax protein expression in two treatment group was obviously expressed.Conclusion FMNP-MSC can accurately target to the tumor area,which heats up to the effective temperature under alternating magnetic field.The growth of tumor in mice was significantly inhibited.Apoptosis and necrosis could be seen in tumor,may be achieved by increasing the expression of Bax.

关 键 词：间充质干细胞 荧光纳米磁性粒子 肺癌 热疗 

分 类 号：R734.2[医药卫生—肿瘤]