磁性纳米氧化铁颗粒在人肝癌Bel7402细胞裸鼠模型中的定向浓集及其生物学效应

目的 研究37 nm左右磁性纳米氧化铁颗粒(MNPs)在外加极低频交变磁场(EMF)作用下对人肝癌细胞株Bel 7402细胞抑制的效果及其机制.方法 用共沉淀法制备粒径为37 nm的MNPs,用尾静脉注射法注入Bel 7402细胞裸鼠模型,用静磁场定位MNPs于荷载肿瘤区,定位完成后用EMF照射病灶区,用磁共振检测静磁场定位MNPs的效果,用流式细胞仪检测肿瘤细胞凋亡及死亡情况,用Western blot方法检测细胞凋亡相关蛋白Bcl蛋白质组的表达.数据处理用单因素方差分析.结果 磁性纳米粒子在肿瘤部位的含量达到98.9%.经EMF照射静磁场定位MNPs裸鼠模型存活时间延长至(27.4±0.7)d,肿瘤抑制率为37.5%±0.8%,此种条件下肿瘤细胞早期凋亡明显,凋亡率为18.1%±0.6%.EMF照射能导致肿瘤细胞凋亡相关Bcl蛋白质组表达明显,EMF照射MNPs静磁场定位细胞Bcl2/Bax的比值(0.07±0.01)与未进行静磁场定位的细胞(0.23±0.02)比较,差异有统计学意义(F=0.016,P＜0.05).结论 EMF照射静磁场MNPs定向浓集人肝癌Bel 7402细胞裸鼠模型能很好的抑制肿瘤增殖,并导致肿瘤细胞发生大量凋亡从而延长裸鼠肿瘤模型存活时间.

Investigation on the migration and biologic effects of nano FeOx powders under the exposure of extremely low frequency altering electric magnetic fiek in human heptoma-bearing nude mice in vivo

Objective To investigate the mechanism and biologic effects of 37 nm magnetic nano FeOx powders (MNPs) on human hepatoma-bearing nude mice. Methods 37 nm MNPs were prepared by coprecipitation methods and then injected into human hepatoma (Bel-7402) bearing-nude mice through the tail vein. After injection of MNPs, the mice were first exposed under static magnetic field and then treated under extremely low frequency altering-electric magnetic field directing to the tumor area. The migration and trafficking of MNPs were determined by MMR. Tumor growth was monitored with calipers every 5 days and rumor volume was calculated on the basis of three-dimensioned measurements. The apoptosis of tumor cells was analyzed by flow cytometry analysis. The expressions of apoptosis-associated proteins Bcl-2, Bax and HSP27 were determined using western-blot analysis. Results Static magnetic field could direct the migration and trafficking of MNPs to the tumor site with a higher ratio of 98.9%. Extremely Low Frequency Electric-Magnetic Field (EMF) treatment could inhibit the proliferation of tumor cells and prolong the survive time of tumor-bearing mice injected with MNPs. In addition, the survival time of tumor-bearing mice and percentages of prohibition on tumor cell growth were 27.4 ± 0.7 days and 37.5 ± 0.8%( F = 0.005, P ＜ 0.05), respectively.The results of flow cytometry analyses showed that about 18. 1士 0.6% ( F = 0.030, P < 0.05) of tumor cells were induced into early apoptosis. Furthermore, expressions of apoptosis-associated proteins Bcl-2 and Bax were significantly induced by MNPs under EMF treatment. The ratio of Bcl/Bax in both MNPs and EMF treatment 0.05). Heat shock protein-27 (Hsp-27) was not significantly induced in different treatment groups. Conclusion Injection of MNPs with EMF exposure on human hepatoma-bearing nude mice could significantly prolong the survival time, inhibit the tumor proliferation and growth. and induce tumor cells into apoptosis.