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目的：研究自杀基因与粒细胞－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）基因联合治疗抗肿瘤作用及免疫机制。方法：小鼠皮下接种黑色素瘤Ｂ１６Ｆ１０细胞３ｄ后，分别在肿瘤局部直接注射表达小鼠ＧＭ－ＣＳＦ的重组腺病毒ＡｄＧＭ－ＣＳＦ和表达大肠杆菌胞嘧啶脱氨酶（ＣＤ）基因的腺病毒ＡｄＣＤ，然后连续１０ｄ腹腔注射５氟胞嘧啶（５ＦＣ）（ＡｄＣＤ／５ＦＣ／ＡｄＧＭＣＳＦ组）、单用ＡｄＣＤ／５ＦＣ组、单用ＡｄＧＭ－ＣＳＦ组、注射对照病毒ＡｄｌａｃＺ／５ＦＣ组或ＰＢＳ组。结果：与接受ＡｄＣＤ／５ＦＣ、ＡｄＧＭ－ＣＳＦ、ＡｄｌａｃＺ／５ＦＣ或ＰＢＳ治疗的荷瘤小鼠比较，经联合治疗后荷瘤小鼠皮下肿瘤结节的生长明显受到抑制，荷瘤小鼠的存活期明显延长（Ｐ＜０．０１）。经ＡｄＣＤ／５ＦＣ／ＡｄＧＭＣＳＦ联合基因治疗后，肿瘤瘤体内或瘤周有大量树突状细胞、ＣＤ８＋Ｔ细胞浸润，黑色素瘤细胞表达ＭＨＣ－Ⅰ和Ｂ７－１分子明显增加，荷瘤小鼠脾细胞对Ｂ１６Ｆ１０黑色素瘤细胞特异性杀伤功能增强。结论：联合应用自杀基因和ＧＭ－ＣＳＦ基因转移可以直接杀伤肿瘤细胞，又可提高机体对肿瘤的免疫应答，两者可协同发挥抗肿瘤作用。
Objective: To study the anti-tumor effect and immune mechanism of suicide gene and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene therapy. METHODS: Mice melanoma B16F10 cells were inoculated subcutaneously for 3 days. The recombinant adenovirus AdGM-CSF expressing mouse GM-CSF and the adenovirus AdCD expressing the CD gene were injected directly into the tumor. Then 5-fluorocytosine (5FC) (AdCD/5FC/AdGMCSF group), AdCD/5FC group alone, AdGM-CSF group alone, AdlacZ/5FC group or PBS group were injected intraperitoneally for 10 days. RESULTS: Compared with tumor-bearing mice treated with AdCD/5FC, AdGM-CSF, AdlacZ/5FC or PBS, the growth of subcutaneous tumor nodules was significantly inhibited in the tumor-bearing mice after combined treatment, and the survival time of the tumor-bearing mice was significantly reduced. Prolonged significantly (P<0.01). After combined gene therapy with AdCD/5FC/AdGMCSF, a large number of dendritic cells and CD8+ T cells were infiltrated into the tumor or in the periphery of the tumor. MHC-I and B7-1 molecules were significantly increased in the melanoma cells. The B16F10 melanoma cell specific killing function was enhanced. Conclusion: The combined application of suicide gene and GM-CSF gene transfer can directly kill tumor cells and increase the body’s immune response to tumors. The two can synergistically exert anti-tumor effects.