抗前列腺干细胞抗原单克隆抗体治疗鼠前列腺癌移植瘤

Experimental observation of Anti-PSCA mAb in treatments of human prostate cancer xenografts in mice

目的 探索鼠源性抗前列腺干细胞抗原单克隆抗体 (Anti PSCAmAb)对裸鼠实体性前列腺癌移植瘤的治疗效果。方法 (1 )BALB/c裸小鼠皮下注射激素非依赖性前列腺癌细胞株PC 3细胞 ,细胞数为 2× 1 0 6/只 ,建立前列腺癌实体性移植瘤的动物模型。 (2 )选择肿瘤体积大小相近的1 0只荷瘤鼠 ,随机分成治疗组 (N1 =5 )和对照组 (N2 =5 )。治疗组荷瘤鼠腹腔注射Anti PSCAmAb2 0 0 μg ,3天一次 ,连续三次 ;对照组使用等量PBS。 (3)观察 5周 ,记录实验鼠存活情况 ,检测血清前列腺特异抗原 (PSA) ,处死存活的裸鼠 ,测量残存肿瘤的重量、体积并计算肿瘤体积抑制率。取肿瘤组织进行光镜及透射电镜检查。结果 治疗组和对照组的裸鼠均存活 ,血清PSA平均值分别为 :(3 2 8± 0 5 5 )ng/ml和 (7 2 6± 0 4 3)ng/ml;平均瘤重分别为 (0 95± 0 1 7) g和 (3 0 8± 0 1 8)g ;肿瘤体积分别为 (1 6 4 5 9± 1 4 0 8)mm3 和 (5 4 8 4 9± 1 9 79)mm3 ,P <0 0 5 ,治疗组与对照组间均有显著性差异。治疗组肿瘤体积抑制率为 6 9 98%。光镜显示治疗组肿瘤组织内出现大片组织坏死性改变 ,并可见大量炎症细胞浸润 ,透射电镜显示肿瘤细胞的凋亡现象。结论 Anti

Objective To explore the inhibitory effects of Anti-PSCA mAb in treatments of human prostate cancer xenografts in mice.Methods Solid tumors in mice were produced by subcutaneous injection with PC-3 cells in the flanks of mice.We picked out 10 mice bearing human prostate cancer xenografts.They were divided into a treatment group(N 1=5)and a control group(N 2=5).200 μg Anti-PSCA mAb was injected into abdominal cavity in the treatment group and PBS in the control group.Anti-PSCA mAb and PBS were administered once a day for three days.The mice survival conditions of two groups were recorded during 5 weeks.The PSA in serum,the tumor weights and dimensions of survived mice were measured.The tumor volume inhibition rate was calculated.Routine pathological slides of tumor tissue were observed under light microscope to evaluate the range of tumor tissues damaged by Anti-PSCA mAb.Ultrastructure was observed with transmission electron microscope.Results The average PSA levels in serum of the two groups were (3.28±0.55) ng/ml and (7.26±0.43) ng/ml respectively.The weights of tumors of the two groups were(0.95±0.17) g and (3.08±0.18) g respectively.The volumes of them were (164.59±14.08)mm 3 and (548.49±19.79)mm 3.There are remarkable differences between the treatment group and the control group(P<0.05).The tumor volume inhibition rate of the treatment group was 69.98%.Pathological examination showed necrosis and plenty of inflammtory cells infiltrated in tumor tissues.Apoptosis was observed by transmission electron microscope.Conclusion Anti-PSCA mAb could significantly inhibit the growth of human prostate cancer xenografts in mice.