HA纳米载体转hGM-CSF基因的HepG2疫苗联合多柔比星抗肝癌作用  

Antitumor effects of HepG2 tumor vaccine transfected hGM-CSF gene mediated by HA nanoparticles combined with doxorubicin

作　　者：赵祺[1] 段晓明[2] 苏小芳 邓彦君 杨陈[5] 贺修胜[6] 

机构地区：[1]南华大学研究生院,湖南衡阳421001 [2]长沙市第四医院消化内科,湖南长沙410006 [3]张家界市人民医院消化内科,湖南张家界427000 [4]怀化市中医医院B超科,湖南怀化418000 [5]湖南环境生物职业技术学院病理学教研室,湖南衡阳421005 [6]南华大学肿瘤研究所,湖南衡阳421001

出　　处：《现代肿瘤医学》2014年第4期732-736,共5页Journal of Modern Oncology

基　　金：湖南省卫生厅科研基金资助项目(编号:B2005-178)

摘　　要：目的:评价HA纳米载体转hGM-CSF基因的HepG2疫苗联合多柔比星治疗肝癌的效果。方法:建立Hu-PBL-SCID HepG2荷瘤小鼠模型,待皮下种植瘤长至100-150mm3时,随机分为5组,每组5只:对照组(PBS);化疗组(多柔比星DOX);疫苗组(60Co照射的转染GM-CSF基因的HepG2细胞);先疫苗后化疗组;先化疗后疫苗组。末次治疗后第5天处死各组小鼠,用MTT法测定脾脏CTL活性及肿瘤组织浸润淋巴细胞(TIL)杀伤活性;取肿瘤组织行HE染色及CD8+T细胞免疫组化检查。结果:化疗组的CTL活性与对照组相比无显著变化(P>0.05)。疫苗组和先疫苗后化疗组及先化疗后疫苗组的CTL活性显著强于上述两组(P<0.05),该3组两两之间也存在显著差异(P<0.05),而先化疗后疫苗组的CTL活性增强最为明显,明显高于其他两组(P<0.05)。该组的TIL活性同样强于其他各组。同其它组相比,先化疗后疫苗组的瘤体内可见大量肿瘤细胞坏死,CD8+T细胞浸润显著增加。结论:HA纳米载体转染hGM-CSF基因的HepG2疫苗的主动免疫联合多柔比星化疗具有协同抗肝癌作用,为肿瘤免疫联合化疗治疗肿瘤提供了实验依据。Objective：To investigate the treatment effects of HepG2 tumor vaccine transfected hGM - CSF gene mediated by HA nanoparticles combined with doxorubicin to liver cancer. Methods： Establish Hu - PBL - SCID HepG2 tumor - bearing mice. When the xenografted to 100 - 150 mm3 , mice were randomly divided into five groups,five rats in each group：control group（ PBS）, chemotherapy group （doxorubicin DOX）, the vaccine group （HepG2 cells transfeeted with GM - CSF gene after 6o Co irradiated）, chemotherapy after the vaccine group, the vaccine after chemo- therapy group. The mice were sacrificed 5d after the final therapy and examined their spleens CTL activity and tumor infiltrating lymphocyte（TIL） activity measured by MTI＇. Tumor tissue was stained by HE and CD8 T cells in the tis- sue was examined by immunohistochemistry. Results： The CTL activity of chemotherapy group had no significant change which compared with control group（P 〉0.05 ）. The CTL activity of the vaccine group and chemotherapy after vaccine group and the vaccine after chemotherapy group were significantly stronger than the above two groups （P 〈 0.05 ）. There were significant differences between the three group（ P 〈 0.05 ） ,while the CTL activity of the vaccine after chemotherapy group increased most significantly, higher than the other groups （ P 〈 0.05 ）. TIL activity of this group has better effect than others. Compared with other groups, more tumor necrosis in tumor specimens and more in- filtration of CD8 ＋ T - lymphocytes in the vaccine after chemotherapy group were observed. Conclusion： The active im- munization of HepG2 tumor vaccine transfeeted hGM - CSF gene mediated by HA nanoparticles combined with the chemotherapy of doxorubicin to liver cancer has synergistic effect for hepatoma,whieh provides the experimental basis for cooperation of tumor immune treatment and chemotherapy.

关 键 词：肝癌 肿瘤疫苗 多柔比星 GM—CSF基因 免疫化疗 

分 类 号：R73-362[医药卫生—肿瘤] R735.7[医药卫生—临床医学]