电穿孔化疗对结肠癌裸鼠移植瘤模型的疗效及免疫机制初探  

Effects and immune mechanisms of electrochemotherapy on human colon cancer xenografts in nude mice.

作　　者：郑民华[1] 冯波[1] 孙骥远[1] 陆爱国[1] 李健文[1] 王明亮[1] 郁宝铭[1] 

机构地区：[1]上海第二医科大学附属瑞金医院普外科上海市微创外科临床医学中心上海消化外科研究所,200025

出　　处：《中国实用外科杂志》2004年第11期681-684,i004,共5页Chinese Journal of Practical Surgery

摘　　要：目的　观察电穿孔技术结合博莱霉素化疗对结肠癌裸鼠移植瘤的抗肿瘤效果 ,探讨其免疫效应机制 ,为其临床应用提供实验依据。方法　 2 0 0 2年 11月至 2 0 0 3年 6月 ,用人结肠癌Lovo细胞系建立结肠癌裸鼠移植瘤模型 ,随机分为电穿孔化疗组 (B +E +)、单纯化疗组 (B +E - )、单纯电击组 (B -E +)和阴性对照组 (B -E - ) ,动态观察肿瘤大小 ,7d后处死并取出皮下肿瘤称重 ,观察其组织学改变 ,并用LDH法检测小鼠脾NK、LAK杀伤活性。结果　B +E +组移植瘤较其他各组明显缩小 (P <0 0 1) ;B +E +组完全缓解 1例 ,部分缓解 7例 ,B -E +和B +E -组内各有 1例部分缓解 ,而B -E -组中无一例有效 ,B +E +组有效率与其余各组的差异有统计学意义 (P <0 0 1) ;组织学观察也显示B +E +组的移植瘤内大片肿瘤细胞坏死、血管损伤和炎细胞浸润 ;各组小鼠的NK和LAK细胞的杀伤活性差异无显著意义 (P >0 0 5 )。结论　电穿孔化疗可显著增强结肠癌裸鼠移植瘤对化疗的敏感性和疗效 ,可能主要与T细胞介导的肿瘤特异性免疫机制有关 ,可成为结肠癌治疗的一种新方法。Objective To evaluate the anti-tumor effects and immune mechanisms of electrochemotherapy(ECT) employing electroporation and bleomycin (BLM) in human colon cancer xenografts in nude mice. Methods Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for three weeks, were allocated randomly into four groups: B+E+(electrochemotherapy), B+E-(bleomycin injected intratumorally), B-E+(electric pulses), and B-E-(no treatment), and tumor volumes were measured daily. The animals were sacrificed on the seventh day, the weight of xenografts were measured, and histology of tumors were evaluated. Cytotoxicity of NK and LAK cells were then assessed by LDH assay. Results The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment( P<0.01). There were one case of complete response(CR) , seven cases of partial response(PR) in group B-E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response rate between group B+E+ and the other three groups was statistically significant (P<0.01). Histologically, extensive necrosis of tumor cells, considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups. Conclusion Electrochemotherapy significantly enhances the chemosensitiviy and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell- dependent, tumor-specific immunity might be involved in the process of electrochemotherapy.

关 键 词：电穿孔化疗 结肠癌 裸鼠 移植瘤 动物模型 免疫机制 

分 类 号：R735.35[医药卫生—肿瘤]