HSV-TK/ACV治疗小鼠肺腺癌LA795及其与机体免疫系统的关系  

Treatment of Mice Lung Adenocarcinoma LA795 by HSV-TK/ACV System and its Realtionship with Immune System

作　　者：姚中强[1] 张梅香[2] 文金序[3] 

机构地区：[1]北京大学人民医院,100046 [2]长治医学院附属和平医院血液内科 [3]广州南方医院

出　　处：《长治医学院学报》2004年第3期165-168,共4页Journal of Changzhi Medical College

摘　　要：目的 :探讨HSV -TK/ACV(GCV)系统对小鼠肺腺癌细胞LA795治疗作用及其与机体免疫系统的关系。方法 :用重组逆转录病毒载体上清感染体外培养的小鼠肺腺癌细胞LA795 ,然后用新霉素类似物G41 8进行筛选 ,得到转染HSV -TK基因的LAtk细胞 ,分别将LA795细胞和LAtk细胞接种于小鼠皮下 ,观察ACV治疗后肿瘤生长情况、抗免疫功能以及对动物生存期的影响。结果 :体外转染HSV -TK基因的LAtk细胞获得了对ACV的敏感性 ,接种LAtk细胞的治疗组动物在ACV治疗后出现了肿瘤体积缩小 ,而对照组接种LA795细胞的动物在ACV治疗后肿瘤体积逐渐增大 ,两者具有显著差异 (P<0 .0 1 )。治疗组动物生存期为 5 1 .8d ,对照组动物生存期平均为 1 5 .9d ,两者具有显著差异 (P <0 .0 1 )。光镜下观察治疗组肿瘤组织及血管周围有大量的淋巴细胞浸润 ,计数 75个高倍视野中的淋巴细胞为 1 1 6.0 3± 5 2 .95 ,而对照组为 1 0 .41± 5 .5 2 ,二者具有显著差异 (P <0 .0 1 )。超微结构观察显示淋巴细胞群攻击癌细胞现象 ,癌细胞出现凋亡征象。结论 :①HSV -TK/ACV系统可以显著杀伤小鼠肺腺癌细胞LA795 ,使肿瘤消退 ,动物生存期延长 ,提示该系统有良好的治疗效果和应用前景。②HSV -TK/ACV系统治疗肿瘤除了其直接杀伤作用外 ,尚有机体免疫系统的?Aim:To study the efficacy of HSV-TK/ACV system in T739 mice bearing lung adenocarcinoma cell LA795 by HSV-TK/ACV system and the relationship between the direct toxicity and the immune system in vivo. Methods: LA795 cells cultured in vitro were infected by recombinant retrovirus vector supernatant ,after G418 selection LAtk cells containing HSV-TK gene were harvested. LA795 and LAtk cells were injected subcutaneously in the T739 mice . After ACV treatment ,the tumor growth , mice life span and the anti-tumor immunity were observed. Result: LAtk cells were susceptibility to ACV. Mice inoculated with LAtk tumor cells presented tumor regression after ACV treatment ,while the control mice inoculated with LA795 presented continous tumor growth (P< 0.01). Life span of the mice treated by HSV-TK/ACV was (51.8±8.68)d, while the control mice was 15.9±5.61(P<0.01).Under light microscopic inspection a large amount of lymphocytes around the tumor and the blood vessels of the experiment group could be seen. TIL number of the experiment group was 116.3±52.95, while the control group was 10.41±5.52(P<0.01).Under electronic microscopic inspection ,tumor cells attackted by groups of TILs could be seen. And tumor cells underwent apoptosis.Conclusion:1.HSV-TK/ACV system can successfully cure mice tumor ,and it shows good clinical prospect. 2.In the theatment of HSV-TK/ACV ,not only its direct toxicity is employed ,but also the immune system is involved.

关 键 词：HSV-TK基因 基因治疗 肿瘤浸润淋巴细胞 免疫 T739小鼠腺癌细胞 

分 类 号：R734.2[医药卫生—肿瘤]