分枝杆菌Ag85B/IL-2融合蛋白对小鼠膀胱癌抑癌效应的研究

Anti-tumor effect of mycobacterium Ag85B/IL-2 fusion protein on syngeneic mice bearing bladder cancer

目的探讨分枝杆菌Ag85B/IL-2融合蛋白对小鼠膀胱癌的抑癌效应。方法采用小鼠T739可移植性膀胱癌模型,共80只分为10组,于移植瘤处局部注射分枝杆菌Ag85B/IL-2融合蛋白,并用Ag85B蛋白、BCG、IL-2和生理盐水作对照,观察治疗后各组的肿瘤质量、体积和存活期。光镜和电镜下观察肿瘤的形态改变。结果分枝杆菌Ag85B/IL-2融合蛋白治疗组小鼠肿瘤瘤质量(2.49±0.60)g,非常显著低于Ag85B蛋白组、BCG组、IL-2组和生理盐水组(P<0.01);Ag85B/IL-2融合蛋白治疗组小鼠肿瘤瘤体积(3.01±0.95)cm3,显著低于Ag85B蛋白组、BCG组、IL-2组和生理盐水组(P<0.05,P<0.01);Ag85B/IL-2融合蛋白治疗组小鼠存活天数(35.50±2.60)d,显著长于Ag85B蛋白组,BCG组、IL-2组和生理盐水组(P<0.05,P<0.01);Ag85B/IL-2融合蛋白对小鼠的肿瘤质量抑制率为64.50%,肿瘤体积抑制率为62.24%,存活延率为48.66%。光镜下观察Ag85B/IL-2融合蛋白治疗组肿瘤细胞有明显的炎性细胞浸润、肿瘤细胞坏死、出血等改变;透射电镜下观察,可见细胞膜破裂,细胞器破坏,细胞质固缩,细胞核破坏,核染色质聚集,凋亡小体出现,巨噬细胞吞噬增多等现象。结论分枝杆菌Ag85B/IL-2融合蛋白对小鼠膀胱癌具有抑制作用,并能延长膀胱癌荷瘤鼠的生存期。

Objective To study the anti-tumor effect of myeobaeterium Ag85B/IL-2 fusion protein on syngenie mice beating bladder cancer. Methods After being implanted BTT739 bladder transitional carcinoma cells from tumor bearing mice, 80 T739 mice were divided into Ag85B protein, BCG, IL-2 and normal saline groups （n =20）. Mycobacterium Ag85B/IL-2 protein was locally injected to the mice at the site of implanting tumor in the trial group, and Ag85B protein, BCG, IL-2 and normal saline to the control group mice. The weight and volume of tumor and the survival period were recorded after treatment. Results The average weight of Ag85B/IL-2 fusion protein treatment group was significantly lower than those of Ag85B, BCG,IL-2 and normal saline group （P 〈 0. 01 ）. The average volume of Ag85B/IL-2 fusion protein treatment group was significantly lower than those of Ag85B, BCG,IL-2 and normal saline group （P 〈0. 05, P 〈0. 01 ）. The average survival period of Ag85B/IL-2 fusion protein treatment group was significantly longer than those of Ag85B, BCG, IL-2 and normal saline group （P 〈0.05, P 〈0.01 ）. The tumor weight and volume inhibition rate of Ag85B/ IL-2 fusion protein were 64.50% and 62.24%, respectively, and the survival period prolonging rate of Ag85B/ IL-2 fusion protein was 48.66%. Under light microscope, the bladder tumor tissue treated by Ag85B/IL-2 presented obviously inflammatory cells infiltrating, neoplasm necrosis, hemorrhage. With transmission electron mi- croscope, the bladder tumor cell membrane was un-integrated, organelles damaged, cytoplasm pycnosis, nucleus fragmentation, aggregation on chromatin, apoptosis body coming up, macrophage swollen and so on. Conclusion The results indicate that mycobactcrium Ag85B/IL-2 protein has obvious anti-tumor effect in T739 mice bearing bladder cancer and can prolong its survival period.