^(188)Re-Herceptin免疫导向治疗乳腺癌的实验研究

^(188)Re-labeled herceptin inhibits proliferation of breast cancer cell line SKBR-3 in vitro

目的以针对HER-2/neu癌基因表达蛋白为靶点的人源性单克隆抗体Herceptin作为靶向载体,制备188Re标记的放射免疫治疗剂(188Re-Herceptin),观察其在体外对HER-2/neu癌基因高表达的SKBR-3乳腺癌细胞株的靶向结合性及抗癌作用。方法188Re对Herceptin的标记采用直接标记法,取不同放射性活度的188Re-Herceptin与SKBR-3乳腺癌细胞共同培养,以MTT法测定其对单层培养的肿瘤细胞生长的抑制作用,并计算相对抑制率(IC50)。结果188Re-Herceptin在体外可明显抑制SKBR-3细胞,且其杀伤作用呈剂量依赖性;而188Re标记的正常鼠IgG(nmIgG)和188ReO4-的抑制作用较弱。188Re-Herceptin组的IC50(76.1×104Bq/L)明显低于188Re-nmIgG组(139.2×104Bq/L)和188ReO4-组175×104Bq/L。结论188Re-Herceptin具有明显的抑制体外培养SKBR-3乳腺癌细胞生长增殖的作用,可进一步用于乳腺癌的放射免疫导向治疗。

Objective To investigate the inhibitory effects of ^188Re-labeled herceptin on the proliferation in vitro of breast carcinoma cell line （SKBR-3） overexpressing HER-2/neu proto-oncogene. Methods Heroeptin was radiolabcled with ^188Re through a direct labeling method. SKBR-3 cells were cultured with ^188Re-Hereeptin at different radioactivity doses （3.7×10^4, 18.5×10^4, 37×10^4, 55.5×10^4 and 74×10^4 Bq/ml） or with ^188Re-nmIgG and ^188ReO4^- for comparison. The cell proliferation inhibition was determined with MTT colorimetric assay. Results ^188Re-Herceptin could markedly inhibit the growth of SKBR-3 cells in a radioactivity dose-dependent fashion, while the effect of ^188Re-nmIgG and ^188ReO4^- showed rather poor inhibitory effect in vitro. The 50% inhibition doses （IC50） of ^188Re-Herceptin, ^188Re-nmIgG and ^188ReO4^- were 76.1×10^4 Bq/L, 139.2×10^4 Bq/L and 175×10^4 Bq/L, respectively. Conclusion ^188Re-Herceptin can effectively inhibit the growth of in vitro cultured breast cancer cells overexpressing HER-2/neu, and shows much potential for clinical use in beast cancer radioimmunotherapy.