【摘要】 目的 探讨条件增殖型腺病毒PSA-ZD55-hTERT对人前列腺癌LNCaP细胞移植瘤端粒酶逆转录酶(hTERT)基因表达和肿瘤生长的抑制作用。方法 建立人前列腺癌LNCaP细胞裸鼠移植瘤模型,瘤体内注射PSA-ZD55-hTERT,定期测量肿瘤体积,免疫荧光检测移植瘤组织中E1A及hTERT表达,原位末端标记法(TUNEL)检测肿瘤细胞凋亡。结果 PSA-ZD55-hTERT能有效沉默hTERT基因,PSA-ZD55-hTERT组hTERT表达水平显著低于Ad-hTERT组、Ad-EGFP组及PBS组,差异显著;Ad-hTERT组、Ad-EGFP组及PBS组细胞凋亡阳性率分别为(49.7±5.1)%、(28.8±4.0)%和(2.8±2.4)%,而PSA-ZD55-hTERT细胞凋亡阳性率为(73.5±6.4)%,表明PSA-ZD55-hTERT能有效诱导肿瘤细胞凋亡;PSA-ZD55-hTERT接种7周后肿瘤体积为(131.5±28.2)mm~3,明显低于Ad-hTERT组[(469.2±74.3) mm~3]、Ad-EGFP组[(583.0±98.5) mm~3]和PBS组[(1547.5±196.4) mm~3]。结论 PSA-ZD55-hTERT对裸鼠人前列腺癌LNCaP细胞移植瘤有显著的治疗效果,为治疗前列腺癌提供新的平台。更多还原

【Abstract】 Objective To investigate the inhibitive effects of conditionally replicative adenovirus PSA-ZD55-hTERT on hTERT gene expression and the growth of human prostatic carcinoma cells in nude mice.Methods A nude mouse of prostatic carcinoma cell model was established where BALB/C nude mice were subcutaneously inoculated with LNCaP cells.Then the tumor-bearing nude mice were intratumorally injected with PSA-ZD55-hTERT.The tumor size was regularly measured.The expression of E1A and hTERT in the tumor tissue was examined using laser scanning confocal microscopy and immunohistochemistry.Meanwhile,the apoptosis of tumor xenografts was measured by in situ end labeling technique(TUNEL).Results The expression of hTERT in the PSA-ZD55-hTERT group was remarkably weakened in comparison with those in the Ad-hTERT,Ad-EGFP and PBS groups.The apoptotic rate was(49.7±5.1) % in the Ad-hTERT group,(28.8 ± 4.0) % in the Ad-EGFP group and(2.8 ± 2.4) % in the PBS group.In contrast,the apoptotic rate was(73.5±6.4)% in the PSA-ZD55-hTERT group.In other words,PSA-ZD55-hTERT could effectively induce cellular apoptosis.The mean tumor size was(131.5±28.2) mm~3 in the PSA-ZD55-hTERT group seven weeks after inoculation,which was significantly smaller than those in the Ad-hTERT group[(469.2±74.3) mm~3)],the Ad-EGFP group [(583.0±98.5) mm~3] and the PBS group [(884.9±52.5) mm~3].Conclusions Conditionally replicative adenovirus PSA-ZD55-hTERT can remarkably inhibit the growth of human prostatic carcinoma cells in nude mice,which provides new evidence for the therapy of human prostatic carcinoma.更多还原