摘要
目的：观察自杀基因与细胞因子基因联合转移的抗肿瘤作用与免疫机制。方法：将表达大肠杆菌胞嘧啶脱胺酶（ＣＤ）的重组腺病毒（ＡｄＣＤ）及表达小鼠粒巨噬细胞集落刺激因子（ＧＭＣＳＦ）基因的重组腺病毒（ＡｄＧＭＣＳＦ）直接进行体内注射，合并应用５氟胞嘧啶（５ＦＣ）对红白血病皮下荷瘤小鼠模型进行治疗。结果：联合基因治疗能显著抑制荷瘤小鼠皮下肿瘤的生长，并明显延长其生存期（Ｐ＜０．０５）；免疫功能检测表明，联合基因治疗组小鼠ＣＴＬ杀伤活性明显高于单用ＡｄＣＤ／５ＦＣ、ＡｄＧＭＣＳＦ、对照病毒ＡｄＬａｃＺ／５ＦＣ或ＰＢＳ治疗组；病理分析显示，联合基因治疗组肿瘤细胞发生明显坏死，瘤内及瘤周有大量的炎性细胞浸润。结论：应用自杀基因与细胞因子基因联合转染可更有效地抑制荷瘤小鼠肿瘤的生长。
Objective:To explore the antitumor effect of combined transfer of suicide gene and GMCSF gene in erythroleukemiabearing mice.Methods: Adenovirus harboring E.coli. cytosine deaminase (CD) gene (AdCD) and/or GMCSF gene (AdGMCSF) were used for the treatment of erythroleukemiabearing mice. The mice were inoculated with FBL3 erythroleukemia cells subcutaneously and 3 days later received AdCD followed by 5fluorocytosine (5FC) treatment with or without AdGMCSF. Results: The mice received AdCD/5FC and AdGMCSF developed tumors more slowly and survived much longer than those received AdCD/5FC alone, AdGMCSF alone, control virus AdLacZ/5FC or PBS. Combined transfer of CD gene and GMCSF gene induced a higher specific CTL activity than control therapies did. Pathological examination illustrated that there were tumor necrosis and massive lymphocyte infiltration in the mice after the combined therapy. Conclusion: Combined transfer of suicide gene and cytokine gene could synergistically inhibit the growth of erythroleukemia cells in the mice and induce tumor specific immunity of the host.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
1998年第6期294-298,共5页
Chinese Journal of Hematology
基金
国家自然科学基金
关键词
红白血病
基因治疗
胞嘧啶脱胺酶
GM-CSF
Gene therapy
Cytosine deaminase
Granulocytemacrophage colony stimulating factor
5 Fluorocytosine
Adenovirus
Erythroleukemia
