载双歧杆菌胞外多糖纳米粒子诱导人胃癌裸鼠移植瘤细胞的凋亡  

Bifidobacterium exopolysaccharide-loaded nanoparticles induces apoptosis of human gastric cancer cells transplanted into nude mice

作　　者：张宇[1] 李玉涛[1] 侯任穷[1] 刘宁[1] 

机构地区：[1]东北农业大学食品学院乳品科学教育部重点实验室,哈尔滨150030

出　　处：《中国肿瘤生物治疗杂志》2008年第2期129-133,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No30371055)~~

摘　　要：目的:制备载双歧杆菌胞外多糖纳米粒子(Bifidobacterium exopolysaccharide-loaded nanoparticles,B.EPS-NPs),探讨B.EPS-NPs对人胃癌细胞裸鼠移植瘤增殖和凋亡的影响。方法:取Fe3O4纳米粒子和B.EPS,采用乳化高温固化法制备B.EPS-NPs。建立人源胃癌细胞(BGC-823)裸鼠移植瘤模型,接种6d后随机分为5组,分别以生理盐水、NPs、环磷酰胺(cytoxan,CTX)、游离B.EPS及B.EPS-NPs进行灌胃治疗。观察各组瘤体的生长情况,TUNEL法检测细胞凋亡,透射电镜观察细胞超微结构,免疫组化法检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)及凋亡调控基因bcl-2、bax蛋白表达水平。结果:空载NPs和B.EPS-NPs平均粒径分别为(560±21)nm、(960±32)nm,B.EPS-NPs载药率为30%。B.EPS-NPs对移植瘤的抑瘤率为(46.4±2.94)%,高于游离B.EPS组的(32.0±1.62)%和NPs组的(4.9±0.98)%。B.EPS-NPs组移植瘤细胞凋亡指数明显高于B.EPS组[(66.8±5.58)%vs(41.3±4.26)%](P<0.01)。透射电镜观察到B.EPS-NPs治疗后的移植瘤细胞核染色质凝集成块状,出现了典型的凋亡特征。与B.EPS相比,B.EPS-NPs组PCNA及bcl-2的表达水平有所降低(P<0.01),bax的表达水平有所提高(P<0.01)。结论:纳米粒子运载B.EPS增强了后者对胃癌细胞(BGC-823)移植瘤的增殖抑制作用和促凋亡作用,提高了B.EPS的抗肿瘤活性。Objective：To prepare Bifidobacterium exopolysaccharide-loaded nanoparticles（B.EPS-NPs）and to investigate the effect of B.EPS-NPs on the proliferation and apoptosis of human gastric cancer cells transplanted in nude mice. Methods： B.EPS and nanoparticles of Fe3O4 were used to prepare B.EPS-NPs by the method of emulsion polymerization. Transplant models of human gastric cancer cells BGC-823 were established in nude mice and were divided into 5 groups after 6 days, namely, the normal saline group, nanoparticle group（NPs）, cytoxan （CTX） group, B.EPS group, and B.EPS-NPs group. The corresponding agents were used for gastric lavage. The growth of tumor was observed and cell apoptosis was detected by TUNEL. The ultra-microstructure of tumor cells was observed under TEM, expression of proli-ferating cell nuclear antigen （PCNA）, bcl-2 and bax was examined by immunohistochemistry method. Results： The diameters of the empty-loaded NPs and B.EPS-NPs were （560±21）nm and （960±32）nm, respectively; the drug-loading capacity of B.EPS was 30%. The growth of the transplanted tumor was inhibited in B.EPS-NPs group, with the inhibitory rate being （46.4±2.94）%, which was higher than that of the B.EPS group（[32.0±1.62]%） and NPs group [（4.9±0.98]%）. The apoptosis index in B.EPS-NPs group （[66.8±5.58]%） was significantly higher than that of the B.EPS group（ [41.3±4.26]%, P〈0.01）. TEM showed typical apoptotic structures in B.EPS-NPs group. Compared with B.EPS group,B.EPS-NPs group had markedly lower expression of PCNA and bcl-2 （P〈0.01） and higher expression of bax （P〈0.01）. Conclusion： Nanoparticles can enhance the inhibitory effect and pro-apoptosis effect of B.EPS for human gastric cancer （BGC-823） transplanted tumor.

关 键 词：纳米粒子 双歧杆菌 胞外多糖 胃癌 凋亡 

分 类 号：R735.2[医药卫生—肿瘤] R730.54[医药卫生—临床医学]