南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (07): 934-.

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131I-CD133mAb联合顺铂在体内外有效抑制人肝癌细胞的生长

陈兴月,侯妍利,段丽群,唐敏,康强强,舒锦,彭志平,李少林   

  • 出版日期:2014-07-20 发布日期:2014-07-20

Inhibitory effect of 131I-CD133mAb combined with cisplatin on liver cancer cells in vitro
and in a tumor-bearing mouse model

  • Online:2014-07-20 Published:2014-07-20

摘要: 目的观察131I-CD133mAb在体内外对高表达CD133抗原的Huh-7人肝癌细胞的靶向抑制作用。方法采用氯胺T法制备
并鉴定131I -CD133mAb;流式检测Huh-7 和HepG2 细胞中CD133 的表达,免疫组化检测瘤体内CD133 的表达;实验设
131I -CD133mAb与顺铂(cisplatin, DDP)联用组、131I-CD133mAb组、DDP组及空白对照组。MTT法检测各组中不同药物处理对
肝癌Huh-7细胞的生长抑制作用和计算每组药物的IC50值。成功构建人肝癌Huh-7细胞移植瘤模型,随机分为4组,1次/2 d给
予尾静脉用药,连续2周,每周测量2次小鼠的体质量,测肿瘤的长径、短径。用药结束后处死小鼠,比较肿瘤的体积、质量,计算
抑瘤率;HE染色法观察肿瘤组织病理学改变。结果131I-CD133mAb抗体标记率为90.25%,放射线化学纯度为97.78%;流式检
测Huh-7 细胞中CD133 的表达为79.53%,明显高于HepG2 细胞;免疫组化结果显Huh-7 细胞CD133 表达明显高于HepG2 细
胞;MTT法检测131I-CD133mAb+DDP组的细胞抑制率及体内抑瘤率明显高于131I-CD133mAb组、DDP组和空白对照组。结论
131I-CD133mAb+DDP在体内体外能有效地抑制高表达CD133抗原的肝癌细胞生长。

Abstract: Objective To study the inhibitory effect of CD133 monoclonal antibody labeled with 131I (131I-CD133mAb) on Huh-7
human liver cancer cell line overexpressing CD133 antigen in vitro and in mouse models bearing the tumor cell xenograft.
Methods 131I-CD133mAb was prepared by chloramines-T method and evaluated for its stability. Flow cytometry and
immunohistochemistry were used to detect the expression of CD133 in Huh-7 cells and in Huh-7 cell-derived tumors,
respectively. Huh-7 cells treated with 131I-CD133mAb plus cisplatin (DDP), 131I -CD133mAb, DDP, or no treatment (blank
control) were examined for cell proliferation suppression by MTT assay with the IC50 calculated. BALB/c mice bearing
subcutaneous Huh-7 cell xenograft in the right forelegs were treated with 131I -CD133mAb, DDP, or both every two days for
two weeks. The tumor size and volume were measured twice a week, and pathological examination of the tumor was carried
out after the treatments. The tumor inhibition rate was calculated and tumor cell apoptosis observed with HE staining. Results
The labeling ratio of 131I-CD133mAb was 90.25% and the radiochemical purity was 97.78%. Huh-7 cells showed obviously
higher CD133 expression than HepG2 cells. 131I-CD133mAb combined with DDP group resulted in a significantly higher tumor
inhibition rate than other treatments in the tumor-bearing mice. Conclusion 131I-CD133mAb can inhibit the growth of liver
cancer cells with a high CD133 expression both in vivo and in vitro.