顺铂联合exosomes瘤苗对小鼠H_(22)肝癌移植瘤的治疗作用及机制  

Efficacy of cisplatin combined with exosomes tumor vaccine in treatment of mice bearing transplanted H_(22) hepatocarcinoma and its regulatory mechanism

作　　者：汪少华[1] 沈宜[1] 杨麟[1] 李静[1] 范维珂[1] 陈黎[1] 

机构地区：[1]重庆医科大学基础医学院病理生理教研室,干细胞与组织工程研究室,重庆400016

出　　处：《第四军医大学学报》2008年第24期2263-2266,共4页Journal of the Fourth Military Medical University

摘　　要：目的:探讨顺铂与Exosomes瘤苗联合应用对小鼠H22肝癌移植瘤的抑制作用及其机制.方法:将接种H22细胞的荷瘤小鼠随机分为对照组,Exosomes瘤苗组,顺铂组,顺铂+Exosomes联合治疗组.15d后处死小鼠,通过称量各小鼠H22移植瘤的质量,计算抑瘤率;电镜观察荷瘤小鼠肿瘤组织超微结构改变;分别称脾质量和胸腺质量,检测荷瘤小鼠脾脏指数和胸腺指数;采用MTT法检测小鼠脾淋巴细胞增殖情况和细胞毒活性;ELISA法检测血清中IL-2,INF-γ的水平.结果:联合治疗组对移植瘤抑制力最强,抑瘤率达64.4%,电镜下可见较为典型的细胞凋亡形态学改变;联合治疗组荷瘤鼠脾指数、胸腺指数分别为(9.96±0.91),(3.51±4.79)mg/g,与对照组相比较明显提高(P<0.01),且脾淋巴细胞增殖能力和细胞毒活性增强(P<0.01);联合治疗组小鼠血清中IL-2,INF-γ水平分别为(421.51±39.17),(39.86±3.15)g/L,与对照组相比差异具有统计学意义(P<0.01).结论:顺铂与Exosomes瘤苗联合应用,能显著抑制小鼠肝癌移植瘤生长,这种作用可能与增强抗肿瘤免疫功能有关.AIM： To investigate the inhibitory activity of cisplatin combined with exosomes tumor vaccine on the growth of transplanted H22 hepatocarcinoma in mice and its regulatory mechanism. METHODS： The mice inoculated with H22 cells were divided into 4 groups at random： control group, exosomes group, cisplatin group and combination group （eisplatin plus exosomes）. Fifteen days later, the mice were killed, then the weight of H22 xenograft tumor was measured and the tumor-inhibiting rate was calculated. Transmission electron microscopy （TEM） was used to observe the ultramicro-structure alterations of H22 xenograft tumor tissue in BALB/c mice. The spleens and thymuses were weighed, and the spleen indexes and thymus indexes were determined. The proliferation and cytotoxicity of splenoeytes were detected by MTT assay. Serum levels of IL-2 and INF-γ were detected by ELISA. RESULTS： The inhibitory activity was the most strong in combination group, with the inhibition rate reaching 64.4%. TEM demonstrated the existence of apoptotic cells and apoptotie bodies in H22 xenograft tumor tissues in combination group. The spleen indexes and thymus indexes of mice bearing tumor in combination group were （9.96 ±0.91） and （3.51 ±4.79） mg/g. Compared with control group, the spleen indexes and thymus indexes in combination group were significantly increased （ P 〈 0.01 ）, and the proliferation and cytotoxicity of spleen lymphocytes were remarkably enhanced （P 〈 0.01 ）. The serum levels of IL-2 and INF-γwere （421.51 ±39.17） and （39.86 ±3.15） g/L in combination group, and the difference was significant compared with the control group （P〈0. 01 ）. CONCLUSION： Combination of cisplatin and exosomes exerts strong inhibitory activity on the growth of transplanted H22 hepatocarcinoma in mice. The effect may be correlated to the enhanced immune activity in mice.

关 键 词：顺铂 EXOSOMES 综合疗法 癌症疫苗 

分 类 号：R730.5[医药卫生—肿瘤] R392.1[医药卫生—临床医学]