摘要
目的探讨依赖乏氧诱导因子(hypoxiainduciblefactor.HIF)依赖性表达的自杀基因治疗系统对肾细胞癌的治疗效果。方法借助DNA重组技术构建HIF依赖性表达的重组腺病毒载体Ad-5HRE/hCMVmp-BCD。用Westernblot检测细菌胞苷脱氨酶(bacterialcytosinedeaminase,BCD)的表达,细胞生长抑制试验检测人肾细胞癌786-0细胞对5-氟胞嘧啶(5-fluorocytosine,5-FC)的敏感性,裸鼠移植瘤试验观察Ad-5HRE/hCMVmp-BCD/5-FC对786-0细胞移植瘤的抑制效应。结果786-0细胞感染Ad-5HRE/hCM-Vmp-BCD后,可诱导BCD蛋白的表达,并显著提高细胞对5-FC的敏感性。裸鼠移植瘤试验结果显示,Ad-5HRE/hCMVmp-BCD/5-FC可抑制肾细胞癌移植瘤的生长。结论HIF依赖性表达的Ad-5HRE/hCM-Vmp-BCD/5-FC自杀基因系统可显著抑制肾细胞癌生长,具有良好的临床应用前景。
Objective： To explore the inhibitory effects of hypoxia inducible factor （HIF） - dependent suicidal gene therapy system on renal cell carcinomas. Methods：The HIF -dependent recombinant adenovirus Ad -5HRE/ hCMVmp- BCD was constructed by DNA recombinant technique. Western blot was used to detect HIF -dependent expression of bacterial cytosine deaminase （BCD）. Cell growth inhibition assay was used to determine the sensitivity of human renal cell carcinoma 786 - 0 cells to 5 - fluorecytosine （5 - FC）. Tumor xenograft growth delay assay was used to evaluate the inhibitory effects of Ad - 5HRE/hCMVmp - BCD/5 - FC on renal cell carcinomas. Results： Western blot analysis demonstrated that HIF- dependent BCD protein expression was achieved in 786 -0 cells infected with Ad-5HRE/hCMVmp -BCD. After infection with Ad -5HRE/hCMVmp -BCD, the Sensitivity of 786 -0 cells to 5 - FC significantly increased. Administration of Ad - 5HRE/hCMVmp - BCD/5 - FC could inhibit the growth of 786 -0 xenografts in nude mice. Conclusion： HIF- dependent suicidal gene therapy system Ad- 5HRE/ hCMVmp - BCD/5 - FC can be used as a powerful therapeutic method for renal cell carcinoma.
出处
《现代肿瘤医学》
CAS
2006年第5期536-539,共4页
Journal of Modern Oncology
关键词
HIF
肾细胞癌
自杀基因治疗
胞苷脱氨酶
HIF
renal cell carcinomas
suicidal gene therapy
bacterial cytosine deaminase
