半相合细胞移植对CT-26结肠癌荷瘤小鼠的抑瘤作用  

Inhibitory effect of semi-compatible cell transplantation on CT-26 colon cancer cells in tumor-bearing mice

作　　者：颛孙雪梅 周庆[2] 孙茂民 ZHUANSUN Xuemei;ZHOU Qing;SUN Maomin(Laboratory Animal Research Center, Medical College of Soochow University, Jiangsu Suzhou 215000;Department of General Surgery, Affiliated Hospital of Jiangsu University, Jiangsu Zhenjiang 212013, China)

机构地区：[1]苏州大学医学部实验动物中心,江苏苏州215000 [2]江苏大学附属医院普外科,江苏镇江212013

出　　处：《江苏大学学报（医学版）》2022年第2期136-140,共5页Journal of Jiangsu University：Medicine Edition

摘　　要：目的:探讨半相合细胞移植的移植物对CT-26结肠癌荷瘤小鼠的抑瘤作用及潜在机制。方法:取C57BL/6小鼠的脾细胞和骨髓细胞作为供体细胞;取18只CB6F1小鼠(受体),随机分成对照组、环磷酰胺组和移植组,每组6只,皮下种植小鼠结肠癌CT26细胞建立荷瘤小鼠模型;然后分别于尾静脉注射0.2 mL生理盐水、环磷酰胺、环磷酰胺+脾细胞+骨髓细胞,连续4周;于不同时间点检测3组小鼠肿瘤体积变化;于2周时取3组小鼠肿瘤、肝脏、小肠和皮肤组织,HE染色观察组织变化;ELISA法检测肿瘤组织中IL-2、IL-4、IL-10、IFN-γ、TNF-α和TGF-β含量;流式细胞术检测移植组3 d、2周、4周时小鼠外周血细胞(H-2Kd/b)嵌合率;结果:2周时,环磷酰胺组和移植组小鼠肿瘤体积明显小于对照组(P均<0.01);与对照组和环磷酰胺组相比,移植组肿瘤组织中IL-2、IL-10、IFN-γ与TNF-α含量明显增高(P均<0.05),IL-4和TGF-β含量明显降低(P均<0.05);与移植3 d时相比,2、4周时移植组小鼠外周血中H-2Kb所占比例显著增加(P均<0.01)。结论:C57BL/6(H-2Kb)小鼠来源的脾细胞和骨髓细胞通过改变CB6F1(H-2Kd/b)小鼠肿瘤部位的免疫微环境,进而发挥抗荷瘤模型小鼠结肠癌效应。Objective:To investigate the effect of grafts transplanted with haploidentical cells on CT-26 colon cancer cells in tumor-bearing mice and its potential mechanism.Methods:The spleen cells and bone marrow cells of C57BL/6 mice were taken as donor cells;18 CB6F1 mice(receptor)were taken and randomly divided into control group,cyclophosphamide group and transplantation group,6 mice in each group,and subcutaneously implanted mouse colon cancer CT26 cells to establish subcutaneous tumor-bearing mouse model;then 0.2 mL of normal saline,cyclophosphamide,cyclophosphamide+spleen cells+bone marrow cells were injected into the tail vein for 4 consecutive weeks;the tumor volumes of the three groups mice were detected at different time points;tumor,liver,small intestine and skin tissues of three groups mice were harvested at 2 weeks,and the pathological changes were observed by HE staining;contents of IL-2,IL-4,IL-10,IFN-γ,TNF-αand TGF-βin mouse tumor tissues were detected by ELISA.The chimerism rate of peripheral blood cells(H-2Kd/b)in the transplantation group at 3 days,2 weeks and 4 weeks was detected by flow cytometry.Results:At the 2-week,the tumor volume in the cyclophosphamide group and the transplantation group was significantly smaller than that in the control group(both P<0.01).Compared with the control group and cyclophosphamide group,the contents of IL-2,IL-10,IFN-γand TNF-αin tumor tissues of the transplantation group were significantly increased(all P<0.05),while the contents of IL-4 and TGF-βwere significantly decreased(both P<0.05).Compared with those at 3-day,the proportion of H-2Kb in peripheral blood of CB6F1 mice was significantly increased at 2-and 4-week(both P<0.01).Conclusion:Splenocytes and bone marrow cells derived from C57BL/6(H-2Kb)mice exerted an anti-colorectal cancer effect on tumor-bearing mice by changing the immune microenvironment of CB6F1(H-2Kd/b)mice.

关 键 词：半相合细胞移植 移植物抗肿瘤 移植物抗宿主 小鼠嵌合体 免疫微环境 

分 类 号：R722.6[医药卫生—儿科]