放射性碘标记特异性溶瘤重组腺病毒KH901在荷人肝癌裸鼠体内的抑瘤作用  

Antitumor Effects of Radioiodine Labeled KH901 On Nude Mice Bearing Hepatoma

作　　者：米彦霞[1,2] 李云春[1] 龙亚红[1] 

机构地区：[1]四川大学华西医院核医学科,成都610041 [2]重庆医科大学附属第二医院

出　　处：《生物医学工程学杂志》2010年第2期389-394,共6页Journal of Biomedical Engineering

基　　金：国家自然科学基金资助项目(30770604)

摘　　要：研究131I标记的特异性溶瘤重组腺病毒KH901的生物活性及131I-KH901对荷人肝细胞肝癌裸鼠肿瘤的抑制作用。采用N-溴代琥珀酰亚胺(NBS)法用131I标记KH901,并采用ELISA法测定粒细胞-巨噬细胞集落刺激因子(GM-CSF)的生物活性;通过给药后荷人肝细胞肝癌裸鼠肿瘤的生长实验观察131I-KH901对肿瘤生长的影响,组织切片观察肿瘤组织形态学变化。结果显示:131I-KH901在肿瘤细胞中表达大量的GM-CSF因子,24 h后,在肿瘤细胞和正常细胞中产生的GM-CSF因子分别为183.27±6.90 pg/ml和20.44±0.77 pg/ml;肿瘤生长观察结果显示,131I-KH901瘤内给药能明显抑制肿瘤生长,抑瘤率为71.3%,显著大于131I组(22.7%)及KH901瘤内给药组(52.7%)(P<0.05),组织形态学观察示,注射131I-KH901后,肿瘤出现大片坏死区。因此,131I-KH901能明显抑制裸鼠体内人肝癌细胞的生长,可望成为腺病毒溶瘤和放射性核素联合治疗肿瘤的新型药物。In order to evaluate the biological activity in vitro and the antitumor effects of 131I-conditionally replicating oncolytic adenovirus KH901 on HepG2 human hepatoma xenografts,the leves of GM-CSF expression were determined by ELISA method.A panel of tumor and normal cells was infected with recombinant adenovirus KH901 at MOI of 10 PPC.The medium was harvested to determine the bioactivity of GM-CSF after 24 hours.Nude mice bearing HepG2 human hepatoma xenografts were given 131IKH901.Antitumor effects were assessed using endpoints of tumor growth delay.The data showed that after 24 hours 131I-KH901 replicated hugely in tumor cells and produced significant amount of GM-CSF 183.27±6.90 pg/ml,while producing very small amount of GM-CSF 20.44±0.77 pg/ml in normal cells.In the treatment of tumor,131I-KH901 showed higher restraint rate（71.3%） compared to 131I（22.7%） or KH901（52.7%）.Therefore,131I-KH901 can inhibit the growth of human hepatoma cell in nude mice and it may be a potential drug for treating liver cancer.

关 键 词：溶瘤腺病毒 KH901 放射性碘 同位素标记 粒细胞-巨噬细胞集落刺激因子 放射性核素治疗 

分 类 号：R817.5[医药卫生—影像医学与核医学] R373[医药卫生—放射医学]