外磁场协同表阿霉素-羧甲基磁性纳米颗粒对膀胱癌体内外的杀伤作用

In vitro and in vivo killing effects of epirubicin- carboxymethly magnetic nanoparticles with external magnetic fields on bladder cancer

目的探讨脉冲外电磁场协同表阿霉素(EPI)-羧甲基葡聚糖氧化铁磁性纳米颗粒(CDMN)对人膀胱癌BIU-87细胞体外增殖活性和裸鼠皮下移植膀胱癌生长及其凋亡的影响。方法用化学共沉淀和氧化还原法制备EPI-CDMN并检测其理化性质,建立膀胱癌BIU-87细胞裸鼠皮下移植瘤动物模型,并设立空白对照组、磁场组、EPI组和EPI-CDMN组作为对照。分别采用噻唑蓝(MTT)比色法、双标流式细胞术、DNA原位末端标记法观察脉冲外电磁场联合EPI-CDMN对BIU-87细胞生长增殖活性和裸鼠皮下瘤生长状况及凋亡的影响。结果EPI-CDMN的直径、比饱和磁化强度分别为8～10 nm、0．22 emu/g。外磁场协同EPI-CDMN可以显著抑制BIU-87细胞增殖,抑制率达(21．82±3．18)%,并诱导细胞发生明显的凋亡,凋亡率为(16．8±3．4)%,均显著高于其他各组(P＜0．05)；裸鼠皮下瘤体积(1．57±0．42)cm^3和重量(2．00±0．21)g,均显著低于其他各组,抑瘤率51．69%和细胞凋亡指数(60．45±6．93)%均明显高于其他各组。结论外磁场可以显著增强EPI-CDMN对膀胱肿瘤的杀伤作用,为抗膀胱肿瘤的磁靶向治疗提供了实验依据。

Objective To investigate the effects of the epirubicin-carboxymethly dextran iron oxide magnetic nanoparticles （EPI-CDMN） combined with with external magnetic fields on human bladder cancer BIU-87 cells proliferation and apoptosis in vitro and subcutaneous xenograft bladder cancer growth of nude mice in vivo. Methods EPI-CDMN were prepared by the chemical coprecipitation and periodate oxidation-borohydride reduction procedures and their physico-chemical properties were detected. The nude model of subcutaneous xenograft bladder cancer was established. The groups of blank control, magnetic fields, EPI and EPI-CDMN were all used as controls. The effects of EPI-CDMN combined with external pulsed electromagnetic fields on human bladder cancer BIU-87 cells proliferation and subcutaneous xenograft bladder cancer growth of nude mice were observed by the methyl thiazolyl tetrazolium technique, double-labeled flow cytometry technique and TUNEL method, respectively. Results The diameter and saturation magnetization of EPI-CDMN was about 8-10 nm and 0.22 emu/g respectively. EPI- CDMN combined with external magnetic fields could significandy inhibit the proliferation of BIU-87 cells and induce cells apoptosis. The growth inhibiting rate and apoptosis rate were （21.82± 3.18）96 and （16.8±3.4）96, and the tumor growth inhibiting rate （51.69%） and the tissue cell apoptosis index （60.45 ± 6.93） 96 were aLl respectively significantly higher than those in other groups （ P〈0.05）. The volume （1.57±0.42） cm^3 and weight （2.00 ± 0.21） g of subcutaneous tumor were significantly less than other groups. Conclusion External electromagnetic fields could significantly enhance the killing effects of EPI-CDMN on bladder tumor in vitro and vivo, which provided an experimental basis for the magnetic targeting therapy of bladder tumor.