腺病毒介导p21^(WAF1/CIP1)基因转移及诱导胃癌细胞凋亡

Apoptosis of human gastric cancer cell line SGC-7901 by p21 gene transduction

目的 :探讨 p2 1WAF1/CIP1基因 (p2 1基因 )过表达对人胃癌细胞恶性表型和细胞凋亡的影响 ,进一步了解p2 1基因对肿瘤细胞的治疗作用。方法 :通过腺病毒介导外源性p2 1基因转移到有 p5 3基因突变的人胃癌细胞系SGC 790 1,对 p2 1基因的表达、细胞生长的抑制与机制和对肿瘤模型的治疗效果进行分析。结果 :外源性 p2 1基因在靶细胞高水平表达显著抑制了胃癌细胞的生长和集落形成 ,流式细胞仪检测显示G1期阻滞并发生了凋亡。瘤内注射Ad p2 1对裸鼠体内移植瘤有一定抑瘤作用。 结论 :p2 1基因可能参与肿瘤细胞凋亡的诱导 ,使 p2 1基因在肿瘤的基因治疗 ,特别是在与其他凋亡诱导因子联合作用的方案中有更好的应用前景。

Purpose:To study the effects of overexpression of p21 WAF1/CIP1(p21 gene) on the malignant phenotype and apoptosis of human gastric cancer cell, to further understand the mechanism of action of the tumor-suppressor gene p21. Methods:An adenoviral expression vector with full length cDNA of p21 gene insert was constructed(Ad-p21) and transfevted into SGC-7901 cells with p53 mutation. The effect of exogenous p21 gene on the growth of SGC-7901 cells was examined in vitro and in vivo.Results:Expression of p21 gene in SGC-7901 cells was confirmed by FCM. The in vitro growth of the Ad-p21 transfected SGC-7901 cells was significantly inhibited (inhibition rate: 82%) as compared to mock (Ad-lacZ) transfected SGC-7901 cells. Colony-forming activity in vitro of Ad-p21 transfected SGC-7901 cells was completely inhibited. Morphologically, the Ad-p21 transfected cells appeared apoptotic which was confirmed by the appearance of pre-G 1 on flow cytometry and DNA fragmentation. The growth of SGC-7901 xenografts in nude mice was retarded by intratumoral injection of Ad-p21. Conclusions:p21 gene participates in the induction of cell apoptosis. Its use for gene therapy of cancer, especially when combined with other apoptosis-inducing agents is promising.