131 I-Rituximab对B细胞淋巴瘤生物学效应的实验研究-东南大学学报医学版

131 I-Rituximab对B细胞淋巴瘤生物学效应的实验研究

单位：1.东南大学,临床医学院,江苏,南京,210009； 2.东南大学附属中大医院,核医学科,江苏,南京,210009； 3.东南大学附属中大医院,血液科,江苏,南京,210009

关键词：放射免疫治疗 B细胞淋巴瘤抗CD20单克隆抗体 131I-Rituximab

分类号：R815, R-33, R733

出版年·卷·期（页码）：2008·27·第三期（157-160）

摘要：

目的:研究131I标记的Rituximab对B细胞淋巴瘤细胞的生物学效应以及对荷人Raji细胞移植瘤裸鼠的放射免疫治疗效果,为放射免疫导向治疗提供实验依据.方法:体外培养人B细胞淋巴瘤细胞系Raji细胞,裸鼠皮下接种Raji细胞成瘤,IODO-GEN法将131I标记于Rituximab,将细胞分为131I-Rituximab组、单纯抗体组、单纯核素组及空白对照组4组,流式细胞仪检测各组Raji细胞凋亡和细胞周期;取30只成瘤裸鼠随机分成高、中、低剂量治疗组及单纯抗体组、单纯核素组、空白对照组6组,进行裸鼠的放射免疫治疗研究.每周测量裸鼠荷瘤大小1次,4周后处死裸鼠,取瘤称重,常规病理分析.结果:131I-Rituximab组凋亡率高于其他各组;131I-Rituximab组细胞周期发生变化,大部分被阻滞在G2期.裸鼠各治疗组与对照组比较,肿瘤生长减慢,肿瘤生长抑制率具有剂量时间依赖性,组织病理学检测显示治疗有效.结论:131I-Rituximab能够诱导Raji细胞凋亡并调控细胞周期,而且可特异性地定位于肿瘤组织,发挥放射免疫导向治疗作用,具有潜在的临床应用价值.

Objective To study the biological response of B-cell lymphoma cells to 131I-labeled Rituximab,and to investigate the therapeutic effect of 131I-Rituximab in lymphoma tumor borne in nude mice,in order to offer experimental evidence for the next radioimmunotherapy.Methods Human B lymphomas cell Raji was cultured in vitro.Raji cell was then inoculated subcutaneously in 30 nude mice.Rituximab was labeled with 131I with IODO-GEN method.The cells were randomized into four groups that were 131I-Rituximab group,rituximab alone,131I alone and blank group.Its effects on apoptosis and cell cycles of Raji cells were determined by cytometry.Nude mice were randomized into six groups while the tumor was 8 mm in diameter:high,moderate and low dose radioimmunotherapy groups,Rituximab alone,131I alone and blank group.The size of the tumor was measured at a 3-day interval and the mice were killed in four weeks after treatment.The tumors were resected and weighed.Results The apoptosis rate measured by Annexin Ⅴ-FITC/PI was higher than that in other groups.Cell cycle alteration occurred in 131I-Rituximab group,and the majority of cells were arrested at G2 stage.As compared to blank group,therapy group had a tumor growth inhibition in a does-and time-dependent manner.The pathological exam proved that the therapy was effective.Conclusion 131I-Rituximab can regulate the cycle of Raji cells and induce the apoptosis.The results indicate that the radioimmunological drug made from anti-CD20 monoclonal antibody and 131I can specifically localize in tumor tissue and ensure radioimmunological targeting therapy,which has a potential clinical value.

参考文献：

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