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目的研究双顺反子逆转录病毒载体介导IL-2基因转导成纤维细胞对小鼠肝癌的治疗作用。方法利用双顺反子逆转录病毒载体pGCEN/IL-2将IL-2基因转导小鼠成纤维细胞NIH3T3,然后将分泌IL-2的成纤维细胞与60Gyγ射线照射的肝癌H22细胞皮下植入三天前5×105或2.2×105肝癌H22细胞皮下注射的BALB/c鼠。结果分泌IL-2的成纤维细胞治疗组能明显增加荷瘤小鼠的生存率(P<0.025),抑制肿瘤生长(P<0.05),在肿瘤植入第70天无肿瘤形成的小鼠再次注射1×106H22细胞仍然不发生肿瘤。51Cr释放试验表明来自照射H22与分泌IL-2成纤维细胞混合液注射的小鼠脾细胞与51Cr标记的H22细胞共培养后,51Cr特异释放明显高于对照组(P<0.05)。结论实验结果表明IL-2基因修饰的成纤维细胞能诱导针对肝癌的特异免疫反应。
Objective To study the effect of bicistronic retroviral vector-mediated IL-2 gene transduction of fibroblasts on hepatoma in mice. METHODS: IL-2 gene was transduced into mouse fibroblast NIH3T3 using bicistronic retroviral vector pGCEN/IL-2. Subcutaneous implantation of fibroblasts secreting IL-2 and H22 cells irradiated with 60 Gy γ-rays was performed. BALB/c mice injected subcutaneously with 5 x 105 or 2.2 x 105 hepatoma H22 cells three days earlier. Results The fibroblasts secreting IL-2 treatment group significantly increased the survival rate of tumor-bearing mice (P<0.025), inhibited tumor growth (P<0.05), and had no tumor formation at the 70th day after tumor implantation. The mice re-injected 1×10 6 H22 cells still did not develop tumors. The 51Cr release assay showed that the specific release of 51Cr was significantly higher in the mouse spleen cells injected with the mixture of irradiated H22 and IL-2 fibroblast-producing cells and 51Cr labeled H22 cells than in the control group (P<0.05). Conclusion The experimental results show that IL-2 gene-modified fibroblasts can induce specific immune responses against liver cancer.