腺病毒介导的FasL基因诱导肺癌细胞凋亡

目的研究外源性FasL基因对人肺癌细胞凋亡的影响以及FasL基因治疗肺癌的可能性.方法构建腺病毒载体介导FasL基因转移到低水平表达FasL的人肺腺癌细胞系A549,逆转录聚合酶链反应(RT-PCR)、流式细胞术(FCM)检测FasL基因的表达,并观察A549肺癌细胞凋亡和生长,对肿瘤生长模型的治疗效果进行分析.结果外源性FasL基因在A549肺癌细胞获得高水平的表达,FasL能显著抑制A549的生长和集落形成,流式细胞仪检测显示细胞G1期阻滞并发生了凋亡.瘤内注射Ad-FasL对裸鼠体内移植瘤有较强的抑瘤作用.结论FasL基因参与了肺癌细胞凋亡的诱导,能抑制肺腺癌细胞的生长,因此该基因在肿瘤的基因治疗上有广泛的应用前景.

Apoptosis of human lung cancer cell line A549 by FasL gene transduction

Objective To study the effect of FasL gene on human lung adenocarcinoma cell lines A549 and possibility of exogenous FasL gene for gene therapy of lung cancer. Methods An adenoviral expression vector with full length cDNA of FasL gene insert was constructed(Ad-FasL) and transfected into A549 cells. The effect of exogenous FasL gene on the growth of A549 cells was examined in vitro and in vivo. Results Expression of FasL gene in A549 cells was confirmed by FCM and RT-PCR.The growth of the Ad-FasL transfected A549 cells in vitro was significantly inhibited by 84% as compared to mock (Ad-LacZ) transfected A549 cells. Colony-forming activity of the Ad-FasL transfected A549 cells in vitro was completely inhibited. The Ad-FasL transfected cells appeared apoptotic which was confirmed by the appearance of pre-G 1 on flow cytometry (FCM). The growth of A549 xenografts in nude mice was retarded by intra-tumor injection of Ad-FasL. Conclusion FasL gene participates in the induction of cell apoptosis. It is promising to use it for gene therapy of cancer.