反义增殖细胞核抗原cDNA对人膀胱癌裸鼠异体移植瘤生长的抑制作用

目的　探讨增殖细胞核抗原 (PCNA)反义cDNA对人膀胱癌裸鼠移植瘤模型生长的影响。　方法　脂质体介导反义PCNA真核表达载体转染人膀胱癌EJ细胞后 ,接种到裸鼠皮下组织 ,观察体内致瘤及生长情况 ;免疫组化检测瘤体PCNA蛋白表达 ,RT PCR分析瘤体PCNA、wt p5 3、c myc基因mRNA水平 ;并进行瘤体病理学评估。 　结果　反义PCNAcDNA导入后 ,EJ细胞体内致瘤活性降低 ,同对照组比较瘤体体积缩小 5 4 .2 3% (P <0 .0 5 ) ,重量减轻 4 2 .5 4 % (P <0 .0 1) ,瘤组织PCNA蛋白及mRNA水平分别减少 6 1.6 2 % (P <0 .0 1)和 72 .13% (P <0 .0 1) ,c myc基因表达下调4 7.34% (P <0 .0 1) ,wt p5 3表达活性无显著性改变 (P >0 .0 5 ) ,瘤体病理学特征改善。 　结论　转导反义PCNAcDNA能有效逆转肿瘤的恶性表型 ,是膀胱癌基因治疗的合理策略之一

Growth inhibition effects of antisense cDNA targeting proliferating cell nuclear antigen gene on nude mice allograft model of human bladder cancer

Objective To explore the growth inhibition effects of antisense cDNA targeting proliferating cell nuclear antigen gene (PCNA) on nude mice allograft models of human bladder cancer. Methods Human bladder cancer EJ cells was transfected by antisense PCNA eukaryotic vector with liposome and was seeded hypopercutaneously on nude mice. The in vivo carcinogenic and growth activities of cancer cells were observed.PCNA protein expression in tumor tissues was detected by immunohistochemistry.The mRNA expression levels of PCNA, wt p53 and c myc in tumor tissues were assayed by RT PCR method.The pathological evaluation of tumor tissues was conducted. Results After transferred by antisense PCNA cDNA, the carcinogenic activity of cancer cells was decreased,the volume and weight of tumors being inhibited by 54.23% ( P <0.05) and 42.54% ( P <0.01) respectively. PCNA protein and mRNA levels in tumor tissues were reduced by 61.62% ( P <0.01) and 72.13 %( P <0.01) respectively. The c myc gene expression was down regulated by 47.34% ( P < 0.01 ).There was no significant change in wt p53 expression level ( P >0.05). The pathological characteristics of tumor tissues were ameliorated. Conclusions The malignant phenotypes of tumor could be effectively reversed by antisense PCNA cDNA transfer,which might be one of the ideal strategies for gene therapy of bladder cancer.