【摘要】 目的探讨¹⁸⁸Re-Herceptin-磁性纳米微粒在外置磁场下对 HER-2/neu 癌基因高表达的SKBR-3乳腺癌细胞的靶向结合性及抗癌作用。方法采用戊二醛交联法使人源性单克隆抗体 Her-ceptin 与磁性纳米微粒交联,用直接标记法制备¹⁸⁸Re-Herceptin 及¹⁸⁸Re-Herceptin-磁性纳米微粒,用羰基铼标记法制备¹⁸⁸Re-磁性纳米微粒。肿瘤细胞体外抑制实验设4个组:¹⁸⁸Re-Herceptin-磁性纳米微粒组、¹⁸⁸Re-Herceptin 组、¹⁸⁸Re-磁性纳米微粒组和¹⁸⁸ReO₄^-组,各组均设3.7×10⁴、18.5×10⁴、37×10⁴、55.5×10⁴、74×10⁴ Bq/ml 5个放射性剂量级别;另设生理盐水对照组。采用四甲基偶氮唑蓝（MTT）法测定各组的抑瘤效应,计算相对抑制率,采用半数抑制放射性浓度(IC₅₀)对各组抑瘤作用进行比较和评价。结果 ¹⁸⁸Re-Herceptin-磁性纳米微粒和¹⁸⁸Re-Herceptin 组对 SKBR-3细胞均有较强杀伤作用,且呈剂量依赖性;而¹⁸⁸Re-磁性纳米微粒和¹⁸⁸ReO₄^-组的杀伤作用较弱。¹⁸⁸Re-Herceptin-磁性纳米微粒组的 IC₅₀（53.1×10⁴ Bq/L）明显低于¹⁸⁸Re-Herceptin 组（76.1×10⁴ Bq/L）;¹⁸⁸Re-磁性纳米微粒组和¹⁸⁸ReO₄^-组的 IC₅₀分别为169×10⁴和175×10⁴ Bq/L,明显高于前2组。结论 ¹⁸⁸Re-Herceptin-磁性纳米微粒和¹⁸⁸Re-Herceptin 均可明显抑制体外培养的 SKBR-3乳腺癌细胞增殖,且前者的抑制作用较后者强。更多还原

【Abstract】 Objective SKBR-3 is a breast carcinoma cell line that has overexpression of HER-2/neu proto-oncogen.The aim of this study was to investigate the inhibitive effects of inununo-magnetite targeting thera- py ¹⁸⁸Re-Herceptin-coated magnetite nanoparticles（MNP）in SKBR-3 in the presence of magnetic field.Meth- ods The Heceptin-MNP and Herceptin were radiolabeled with ¹⁸⁸Re by a direct labelling method,and the histi- dine-MNP was radiolabeled with ¹⁸⁸Re(¹⁸⁸Re-MNP)by means of fac-[¹⁸⁸Re（CO）₃（H₂O）₃]⁺as a precursor.By applying a directional external magnetic field with 0.5 T across a 96-well plate containing SKBR-3 cells,the cells were incubated respectively,with ¹⁸⁸Re-Herceptin-MNP,¹⁸⁸Re-Herceptin,¹⁸⁸Re-MNP and ¹⁸⁸ReO₄^- with different radioactivity dose（3.7×10⁴,18.5×10⁴,37×10⁴,55.5×10⁴ and 74×10⁴ Bq/ml）.The inhibition was determined with 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyhe-trazolium bromide（MTT）col- orimetric assay.Results The 50% inhibition doses(IC₅₀)of¹⁸⁸Re-Herceptin-MNP,¹⁸⁸Re-Herceptin, ¹⁸⁸Re-MNP and ¹⁸⁸ReO₄^-were 53.1×10⁴,76.1×10⁴,169×10⁴ and 175 R 10⁴ Bq/L.Conclusion Though both ¹⁸⁸Re-Herceptin-MNP and ¹⁸⁸Re-Herceptin can effectively inhibit the growth of tumor cells, ¹⁸⁸Re-Herceptin-MNP seems to be more suitable for immuno-magnetite targeting therapy in HER-2/neu posi- tive breast cancer patients in the future.更多还原