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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 investigate the enhancing effect of hypoxic targeting suicide gene therapy system on radiation therapy of pancreatic cancer. Methods Recombinant adenovirus vector Ad-5HRE / hCMVmp-BCD with hypoxia-dependent expression was constructed by DNA recombinant technology. FCM was used to detect the expression of bacterial cytidine deaminase (BCD). The cell growth inhibition assay was used to detect the sensitivity of 5-fluorocytosine (5-FC) to human pancreatic cancer MIA-PACA2 cells. The killing effect of 5HRE / hCMVmp-BCD / 5-FC alone or in combination with radiotherapy on MIA-PACA2 cell xenografts. Results After hypoxia treatment, MIA-PACA2 cells infected with Ad-5HRE / hCMVmp-BCD induced the expression of BCD protein and significantly increased the sensitivity of cells to 5-FC. Transplantation of nude mice results showed that Ad-5HRE / hCMVmp-BCD / 5-FC and radiation therapy can inhibit the growth of pancreatic cancer transplanted tumor, but the combination of the two can significantly enhance the inhibitory effect on xenograft tumors. Conclusion The hypoxic-targeted Ad-5HRE / hCMVmp-BCD / 5-FC suicide gene system can significantly enhance the radiotherapy effect of pancreatic cancer cells and has a good clinical application prospect.