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目的探讨硼替佐米(bortezomib,BTZ)对放射治疗U87胶质瘤裸鼠移植瘤的增敏作用和细胞周期分布的影响。方法建立裸鼠U87胶质瘤模型。造模成功的裸鼠随机分为4组:空白组(C)、照射组(RT)、硼替佐米组(BTZ)和联合组(BTZ+RT),裸鼠经8 MeV-β线照射治疗,联合组在照射基础上分别经腹腔注射BTZ,剥离瘤组织,称量计算抑瘤率,测定细胞周期分布、肿瘤生长延迟时间(TGD)、放射增敏比(SER),并比较各组裸鼠平均生存时间。结果 BTZ+RT组抑瘤率为46.5%,优于RT组的31.5%(F=25.6,P<0.01);BTZ+RT组生长延迟时间(TGD)长于RT组(59 d vs 38 d,P<0.01),BTZ+RT使单独放疗的敏感性提高1.44倍;RT联合应用BTZ后,G0/G1期细胞比例下降(79.9%vs 66.0%,P<0.01),G2/M期细胞比例显著提高(3.2%vs 16.4%,P<0.01);BTZ联合RT对小鼠生存时间也有较大改善。结论BTZ对放射治疗U87胶质瘤具有明显的增敏效应,能够有效逆转放射所致细胞G0/G1期进程阻滞,提高G2/M期细胞比例,延长带瘤小鼠生存时间。
Objective To investigate the effects of bortezomib (BTZ) on the sensitization and cell cycle distribution of irradiated U87 glioma xenografts in nude mice. Methods U87 glioma model was established in nude mice. Nude mice were randomly divided into 4 groups: blank group (C), radiation group (RT), bortezomib group (BTZ) and combination group (BTZ + RT) . The combination group was injected with BTZ on the basis of irradiation, the tumor tissue was peeled off, the tumor inhibition rate was weighed, the cell cycle distribution, tumor growth delay time (TGD) and radiosensitization ratio (SER) were measured. Mean survival time of rats. Results The tumor inhibition rate in BTZ + RT group was 46.5%, which was significantly better than that in RT group (F = 25.6, P <0.01). The growth delay time (TGD) in BTZ + RT group was longer than that in RT group <0.01). BTZ + RT increased the sensitivity of radiotherapy alone by 1.44 times. After BT combined with BTZ, the proportion of cells in G0 / G1 phase decreased (79.9% vs 66.0%, P <0.01) (3.2% vs 16.4%, P <0.01). BTZ combined with RT significantly improved the survival time of mice. Conclusion BTZ has a significant sensitizing effect on radiation-treated U87 glioma, which can effectively reverse the process of G0 / G1 arrest induced by radiation and increase the proportion of cells in G2 / M phase and prolong the survival time of tumor-bearing mice.