野生型P53基因对人肠癌细胞株的抑瘤效应

The Antitumorigenic Effects of Wild-Type p53 Gene on Human Colon Adenocarcinoma Cells

为了探讨野生型P53基因对人肠癌细胞株的抑瘤效应。用电穿孔方法将正向携带有野生型P53基因cDNA全长的反转录病毒重组质粒(Dol p53)导入有P53基因突变的人肠癌SW1116细胞,通过标记基因NeoR筛选带外源P53基因的G418抗药性克隆,以观察抗药性克隆数量,同时对G418抗性细胞的生长速度及细胞增殖周期等方面进行观察,结果表明:导入WT-P53基因能使肠癌SW1116细胞的G418抗药性克隆形成减少,细胞生长速度较对照细胞明显减慢,细胞增殖周期G1期增加、S期下降。结果证明人野生型P53基因对肠癌细胞有明确的抑瘤效应,说明基于恢复P53肿瘤抑制基因功能的基因治疗在治疗结直肠癌方面有广阔应用前景。

To gain more insight into the functional role of wild-type and mutant p53 in human coionic carcinoma,we performed experiments to transfer wild-type p53 cDNA into human colon adenocarcinoma cell line (SW1116) harboring mutant p53 genes with re-combinant retroviral vector (Dol-p53). We assessed G418-resistant clonal growth, cell growth properties, soft agar colony formation assay, tumorigenesis in nude mice and cell cycle pattern by flow cytometry. The results demonstrated that human wild-type p53 gene might suppress the phenotype of SW1116 cell line, including inhibition of proliferative activity in culture,an-chorage-independant growth and tumorigenecity. So gene therapy based on restoration of the defective or mutant p53 function will eventually play an important role in the treatment of colorectal cancer.