野生型p53基因的导入对膀胱癌细胞抑制作用的观察

INHIBITION OF HUMAN URINARY BLADDER CANCER CELL GROWTH BY TRANSFECTION OF WILD TYPE p53 GENE

转染外源野生型ｐ５３基因对膀胱癌ＥＪ细胞的抑制作用。方法将含外源野生型ｐ５３基因的（ａｄ┐Ｗｔｐ５３）转染膀胱癌ＥＪ细胞，观察生长曲线，细胞周期变化及裸鼠体内抑瘤试验。结果转染了ａｄ┐Ｗｔｐ５３的ＥＪ细胞在体外生长速率下降，在裸鼠体内致瘤性丧失，流式细胞仪显示，ＤＮＡ合成前期或静止期的细胞比例增高。另外，ａｄ┐Ｗｔｐ５３直接注射到肿瘤组织内，可使外源野生型ｐ５３基因在肿瘤细胞内有效、稳定的表达，肿瘤表现为生长减缓，最后停止生长并有缩小。结论腺病毒载体介导基因转染效率高，速度快，安全，是很有前途的体内基因治疗载体。

Objective:Inhibition of human urinary bladder cancer cell by wild type p53 gene was investigated.Methods:A replication deficient adenovirus vector encoding a wild type p53 (ad Wtp53) was constructed.Results:The pretreatment of cultured human urinary bladder carcinoma cell line EJ with recombinant p53 adenovirus expressing wild type p53 were able to suppress their growth in vitro and their tumorigenicity in nude mice.Introduction of wild type p53 into EJ resulted in increasing proportion of cells in the G 0/G 1 phase of the cell cycle as compared to untransfected cells.Furthermore,exogenous wild type p53 can efficiently transfect into human bladder cancers formed in nude mice via direct intratumor injection as confirmed by immunohistochemical staining.The gene therapy of established human bladder xenograft cancers in nude mice by ad Wtp53 resulted in regression of treated tumors.Conclusion:The results demonstrated the potential of adenovirus mediated p53 gene therapy for human urinary bladder cancer.