~188Re-抗CEA单克隆抗体与白细胞介素12基因抗结肠癌协同效应  

The synergetic effect of ~188Re-anti-CEA-McAb and interleukin 12 gene in colon cancer therapy

作　　者：邢春根[1] 刘增礼[2] 钱建新[3] 俞秋新[3] 周丽英[3] 吾为一[2] 范我[4] 

机构地区：[1]苏州大学附属第二医院普外科,215004 [2]苏州大学附属第二医院核医学科,215004 [3]苏州大学附属第二医院检验科,215004 [4]苏州大学放射医学与公共卫生学院

出　　处：《中华核医学杂志》2005年第6期362-364,共3页Chinese Journal of Nuclear Medicine

基　　金：江苏省卫生厅医学科技发展基金(H200347)

摘　　要：目的在非免疫缺陷荷结肠癌动物模型上观察^(188)Re-抗癌胚抗原(CEA)单克隆抗体(C50)与白细胞介素12(ILl2)基因抑制肿瘤生长的协同作用。方法建立小鼠荷结肠癌动物模型,随机分组后分别施以化疗(CT)、^(188)Re-C50放射免疫治疗(RIT)、IL12基因治疗(GT)及 RIT 与 IL12GT 联合治疗,治疗后3周比较上述各组及对照组(注射生理盐水)的抑瘤效果,同时采用酶联免疫吸附法检测 GT、RIT 及 GT+RIT 3组血清 IL12水平;并于治疗6 h 时采用流式细胞仪检测3组小鼠肿瘤不同周期细胞比率。结果不同治疗后3周各组肿瘤体积、质量比较示,RIT 组与 RIT+GT 组肿瘤体积和质量均明显低于 CT 组和对照组(P<0.01),RIT、RIT+GT 两组间差异有显著性(P<0.01)。血清 IL12水平以 RIT+GT 组最高,与 GT 和 RIT 两组相比差异有显著性(P<0.01)。RIT、GT 和 RIT+GT 3组肿瘤 S 期细胞分别占10.41%、27.53%和6.25%,G_0～G_1期细胞分别占68.60%、53.54%和72.21%;而对照组分别为33.14%和35.12%。结论 ^(188)Re-C50与 IL12基因联合可有效抑制肿瘤生长,疗效优于单独 CT、RIT 及 IL12 GT;RIT+GT 可明显降低肿瘤 S 期细胞比率,并增加 G_0～G_1期细胞比率;^(188)Re-C50可上调 IL12基因表达。Objective To observe the synergetic anti-tumor effect of ^188Re-anti-carcinoembryonic antigen （CEA）-monoclonal antibody （C50） and interleukin （IL） 12 gene on the mice bearing colon cancer. Methods After established the tumor model, chemotherapy （ CT ） , ^188Re-C50 radioimmunotherapy （ RIT ） , IL12 gene therapy（GT） and GT combined with RIT （GT ＋ RIT） were given in each group. Their anti-tumor effect was compared by measuring tumor volume and weight. The proportion of S, Gl phase tumor cells was examined by flow cytometry （FCM）. Meanwhile, the serumal levels of IL12 in RIT, GT and RIT ＋ GT groups were measured by enzyme-linked immunosorbent assay （ ELISA）. Results Three weeks after treatment tumor volume and weight in RIT and GT ＋ RIT groups were significantly lower than that in control and CT goups （ P 〈0.01 ） ; the obvious difference existed between RIT and RIT ＋ GT groups. Apoptotic sub-G1 peak could be observed in FCM histogram 6 h later after RIT, GT and GT ＋ RIT. The S phase ratios of tumor cells in RIT, GT, GT ＋ RIT and control groups were 10.41%, 27.53%, 6.25% and 33.14%, respectively. The G0 - G1 phase ratios of tumor cells in RIT, GT, GT ＋ RIT and control groups were 68.60%, 53.54%, 72.21% and 35.12%, respectively. The serum level of IL12 was highest in RIT ＋ GT group, and the obvious differences existed also between RIT, GT and RIT ＋ GT groups （ P 〈 0.01 ）. Conclusions lss Re-C50 RIT combined with ILl2 GT can inhibit the growth of colon cancer more effectively in tumor-bearing mice than other therapies, thereby, it shows synergetic anti-tumor effect on colon cancer. RIT ＋ GT can increase the G0 - G1 phase ratio of tumor cells but decrease the S phase ratio of tumor cells. Apparently, ^188Re-C50 can up- regulate the expression of IL12 gene.

关 键 词：结肠肿瘤 抗体 单克隆 癌胚抗原 白细胞介素类 药物协同作用 

分 类 号：R735.35[医药卫生—肿瘤]