目的:RA538是从维甲酸诱导终末分化的人食管癌细胞系中分离出的一个与分化相关的基因,本研究探讨了其抗癌作用.方法:利用腺病毒介导基因转移观察对肿瘤细胞的抑制效应.结果:通过重组体腺病毒将RA538基因转导到人肺腺癌细胞系(GLC-82)和人结肠癌细胞系(HCY)中,获得较高的转导效率,显示出较明显的抑制肿瘤生长作用,抑制率分别为77.2%和77.9%,并能降低两细胞系体内肿瘤形成能力.流式细胞计数、DNA片段化分析及TUNEL检测证实RA538可诱导肿瘤细胞发生凋亡.Westem blot分析表明,RA538具有明显下调c-myc基因表达的作用,结论:研究结果提示,RA538是一个较广谱的抑癌基因,可以作为肿瘤基因治疗的一个新目的基因,具有良好的应用前景.

Objective: RA538 is a differentiation-relating gene isolated from a human esophageal cancer cell line which is terminally differentiated induced by retinoic acid. In the present study, the functions of and-tumor of RA538 gene are investigated. Methods: The transfeution of RA538 gene, the effects of inhibition on tumor cells were observed. Results: The transfection of RA538 gene into human lung adenocarcinoma cell line (GLC-82) and colon carcinoma cell line (HCT) by recombined adenovirus results in a fairly high transfection efficiency, showing an obvious suppression to tumor growth (suppression rate: 77 .2 % and 77 . 9% respectively) and a reduction of tumor forming ability of the two cell lines in vivo. FCM.DNA fragmentation analysis and TUNEL domonstrate RA538 can induce apoptosis of tumor cells. Western blot analysis shows that RA538 downregulated c-myc gene expression. Conclusion: The results suggest that RA538 could be a new tumor suppresser gene in tumor gene therapy.

国家863高科技发展基金资助(批准号Z20-01-02)