乏氧靶向性自杀基因治疗系统增强胰腺癌放疗效果的实验研究  

Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy on pancreatic cancer

作　　者：刘军叶[1] 郭鹞[1] 郭国祯[1] 

机构地区：[1]第四军医大学军事预防医学系放射医学教研室,西安710032

出　　处：《国际放射医学核医学杂志》2006年第3期168-172,共5页International Journal of Radiation Medicine and Nuclear Medicine

摘　　要：目的探讨乏氧靶向性自杀基因治疗系统对胰腺癌放射治疗的增强效应。方法借助DNA重组技术构建乏氧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(BCD)的表达,细胞生长抑制实验检测人胰腺癌MIA-PACA2细胞对5-氟胞嘧啶(5-FC)的敏感性,裸鼠移植瘤实验观察Ad-5HRE/hCMVmp-BCD/5-FC单独或联合放射治疗对MIA-PACA2细胞移植瘤的杀伤效应。结果MIA-PACA2细胞感染Ad-5HRE/hCMVmp-BCD后,乏氧处理可诱导BCD蛋白的表达,并显著提高细胞对5-FC的敏感性。裸鼠移植瘤实验结果显示,Ad-5HRE/hCMVmp-BCD/5-FC与放射治疗均可抑制胰腺癌移植瘤的生长,但两者联合可显著增强对移植瘤的抑制效应。结论乏氧靶向性的Ad-5HRE/hCMVmp-BCD/5-FC自杀基因系统可显著增强胰腺癌细胞的放疗效果,具有良好的临床应用前景。Objective To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase （BCD）. Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine （5-FC）. Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-SHRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-CD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy.

关 键 词：细胞低氧 胰腺肿瘤 基因表达调控 肿瘤 胞苷脱氨酶 放射疗法 

分 类 号：R735.9[医药卫生—肿瘤]