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目的 观察体外转mIFN β基因的B16细胞的体内致瘤性和瘤苗作用 ,及通过腺病毒载体介导的mIFN β对体内局部肿瘤治疗和抗肿瘤转移的作用 ,并对其机制进行探讨。方法 利用人类复制缺陷型重组腺病毒将目的基因mIFN β经体外、体内两种途径导入小鼠黑色素瘤细胞 (B16细胞 )中。结果 ①携带目的基因的重组腺病毒感染B16细胞能获得较高的转移效率和目的基因的有效表达 ;②将mIFN β基因导入B16细胞对B16细胞的体外增殖能力无明显影响 ,但能显著提高细胞表面MHC Ⅰ类抗原的表达 ;③将转mIFN β基因的B16细胞接种小鼠 ,其体内致瘤性明显降低 ,且对野生型B16细胞的致瘤性有抑制作用 ;④瘤体内注射和经尾静脉注射途径给予AdCMVmIFN β ,对局部肿瘤和转移瘤有治疗作用。该结果提示 ,利用腺病毒载体携带有效的目的基因来开发瘤苗和治疗肿瘤具有良好的临床应用前景。
Objective To observe the in vivo tumorigenicity and tumor-infecting effects of mIFNβ gene in B16 cells, as well as the role of mIFN β in the treatment of local tumors in vivo and anti-tumor metastasis, and to explore its mechanism. Methods Human replication-defective recombinant adenoviruses were used to introduce the target gene mIFNβ into mouse melanoma cells (B16 cells) via both in vitro and in vivo routes. Results 1 Recombinant adenovirus carrying the target gene infects B16 cells can obtain high metastasis efficiency and effective expression of the target gene; 2 The introduction of mIFN β gene into B16 cells has no obvious effect on the proliferation of B16 cells in vitro, but it can significantly increase the cell number. Expression of surface MHC class I antigens; 3 Inoculation of mice with BIFN-β gene transfected with BIFN-β1 gene significantly reduced the tumorigenicity in vivo and inhibited the tumorigenicity of wild-type B16 cells. 4 Intratumoral injection and via tail Intravenous injection of AdCMVmIFNβ has therapeutic effects on local tumors and metastases. The results suggest that the use of adenoviral vectors carrying effective genes of interest to develop tumor vaccines and treat tumors has good clinical application prospects.