TRAIL和ACNU对实验性大鼠脑胶质瘤的治疗作用  

Therapeutical Effects of TRAIL and ACNU in an Experimental Rat Glioma Model

作　　者：李学元[1,2] 张连群 张学广 马翔宇[2] 赵鹏[2] 李新钢[2] 

机构地区：[1]聊城市脑科医院神经外科,山东聊城252000 [2]山东大学齐鲁医院神经外科,山东济南250012

出　　处：《中国神经肿瘤杂志》2009年第4期241-246,共6页Chinese Journal of Neuro-Oncology

基　　金：山东省卫生系统杰出学科带头人基金资助项目(2003-17)

摘　　要：背景与目的:有研究证明体外条件下肿瘤坏死因子相关的凋亡诱导配体(tumor necrosis factor-related apoptosis inducing ligand,TRAIL)与化疗药物联合应用促进肿瘤细胞的凋亡,但体内的研究却较少报道。本研究观察TRAIL和嘧啶亚硝脲(ACNU)对实验性大鼠脑胶质瘤的治疗作用,并进一步研究TRAIL和ACNU在其联合作用诱导细胞凋亡中影响作用的机制。方法:制备Wistar大鼠C6细胞胶质瘤动物模型,10天后将动物随机分成4组:TRAIL+ACNU治疗组(A组)、ACNU治疗组(B组)、TRAIL治疗组(C组)、生理盐水对照组(D组)。各组经治疗10天后,观察动物的生存状况,动物处死后行肿瘤大体观察、测量肿瘤的体积、计算肿瘤的抑制率;TRAILR2/DR5免疫组织化学表达变化情况;电镜观察肿瘤细胞变化;流式细胞仪检测肿瘤细胞凋亡情况。结果:A组与B组的生存状态较好,而C组与D组的生存状态差。肿瘤体积分别为A组(19.00±2.59)mm3、B组(68.76±5.56)mm3、C组(230.31±13.94)mm3、D组(238.84±10.64)mm3。A、B组与C、D组比较差异有显著性意义(P<0.01)。A组与B组相比差异有统计学意义(P<0.05),C组与D组相比差异无统计学意义;电子显微镜观察,A组和B组可见明显凋亡小体,C组与D组少见。肿瘤细胞凋亡率A组(20.38±1.62)%大于B组(14.85±2.41)%,差异有统计学意义(P<0.05);C组(0.44±0.21)%与D组(0.35±0.24)%相比较差异无统计学意义(P>0.05);A、B组与C、D组相比较差异有统计学意义(P<0.01)。结论:ACNU引起肿瘤细胞凋亡,并可诱导大鼠脑胶质瘤细胞表达DR5,使其对TRAIL诱导的凋亡敏感,二者体内联合应用具有协同作用。BACKGROUND ＆ OBJECTIVE： Glioma cells are generally resistant to chemotherapy, in this study. We evaluated the therapeutical effects of TRAIL and ACNU on neurogliocytoma in an experimental rat model, and further investigated the mechanism of synergistic effects in inducing tumor-cell apoptosis. METHODS： Glioma animal model was established by injecting C6 cells into the right eaudate putamen of Wistar rats. Rats were randomly dMded into 4 groups 10 days after injection, and were treated with TRAIL and ACNU （Group A）, ACNU （Group B）, TRAIL（Group C）, and control group with nomlal saline（Group D） respectively. The rats were killed ＇after 10 days after the treatment. The behaviors of experimental animals were observed. Inhibition ratio of tumor cells was calculated. Expression of TRAILR2/DR5 was analyzed with immtmohistochenistry. Percentage of apoptotic cells was evaluated with flow eytometry. RESULT： The survival condition of Group A and B was better than that of Group C and D. The gross tumor volume was 19.00±2.59 mm3 in Group A, 68.76±5.56 mm3 in Group B, 230.31 ±13.94 mm3 in Group C and 238.84±10.64 mm3 in Group D. Significant differences were found between Group A, B and Group C, D （P〈 0.01）, also between Group A and Group B （P〈 0.05）. There was no difference between Group C and Group D. More apoptotic bodies were observed in Group A and Group B than in Group C and D under electron microscope. The apoptosis rate was （20.38±1.62）% in Group A, （14.85±2.41）% in Group B, （0.44±0.21）% in Group C and （0.35 ±0.24）% in Group D. CONCLUSIONS： ACNU can cause apoptosis of tumor cells and also induce neurogliocytoma cells to express DR5, which makes tumor cells sensitive to apoptosis induced by TRAIL. ACNU and TRAIL have synergistic effect in vivo.

关 键 词：脑胶质瘤 TRAIL ACNU 凋亡 DR5 

分 类 号：R739.41[医药卫生—肿瘤]