联合应用IL-2和IL-3的基因疗法增强骨髓移植后骨髓细胞毒活性及抗肿瘤效果的实验研究

The experimental study on the cytotoxicity and antitumor effects of bone marrow cells in tumor bearing mice receiving syngeneic bone marrow transplantation after IL 2 and IL 3 gene therapy

目的：探讨联合应用成纤维细胞介导ＩＬ２和ＩＬ３的基因疗法对骨髓移植（ＢＭＴ）后荷瘤小鼠抗肿瘤作用的效果及机理。方法：将分别转染ＩＬ２基因及ＩＬ３基因的ＮＩＨ３Ｔ３细胞以单独或联合方式移植至ＢＭＴ的荷瘤小鼠腹腔内８ｄ后，取出小鼠骨髓细胞检测杀伤活性的变化以及ＩＬ２受体的表达，并观察荷瘤小鼠的存活期。结果：ＩＬ３基因治疗虽然可加速ＢＭＴ后造血重建过程，但对骨髓细胞的ＮＫ、ＬＡＫ活性具有一定的抑制作用；ＩＬ２基因治疗可明显提高骨髓细胞的杀伤活性；联合应用基因治疗后荷瘤小鼠骨髓ＮＫ、ＬＡＫ活性及骨髓细胞ＣＤ２５表达升高，明显延长大剂量化疗后接受ＢＭＴ的荷瘤小鼠的存活期。结论：联合应用ＩＬ２和ＩＬ３的基因疗法能协同提高骨髓细胞ＩＬ２受体表达水平，提高骨髓细胞毒活性，增强ＢＭＴ后的抗肿瘤效果。

Objective:To determine the antitumor effects of fibroblast mediated IL 2 gene therapy combined with IL 3 gene therapy in the tumor bearing mice receiving syngeneic bone marrow transplantation (BMT) and investigate their mechanisms.Methods:NIH3T3 IL 2 and NIH3T3 IL 3 encapsulated in collagen were i.p. implanted into the tumor bearing mice which had received syngeneic BMT followed by high dose chemo therapy. Eight days later, the cytotoxicity and IL 2 receptor(CD25)expression of bone marrow cells from the treated mice in different times was detected and the survival time of tumor bearing mice was observed.Results:After the treatment ,the hematopoietic reconstruction was accelerated,the CD25 expression on bone marrow cells was increased and the cytotoxicity of bone marrows cells was suppressed after IL 3 gene therapy. However the NK and LAK activities were augmented and the tumor growth was inhibited markedly after IL 2 gene therapy. Both the cytotoxicity and CD25 expression of the bone marrow cells were increased more significantly,and the survival of the tumor bearing mice was prolonged markedly in combined application of IL 2 gene therapy and IL 3 gene therapy.Conclusion:The data suggest that combined usage of IL 2 gene therapy and IL 3 gene therapy could enhance the CD25 expression on bone marrow cells and augment their cytotoxicity, and then improve the antitumor effects of the tumor bearing mice after syngeneic BMT.