[1]刘军叶,郭鹞,郭国祯.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[J].国际放射医学核医学杂志,2006,30(3):168-172.
　LIU Jun-ye,GUO Yao,GUO Guo-zhen.Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy on pancreatic cancer[J].International Journal of Radiation Medicine and Nuclear Medicine,2006,30(3):168-172.
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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(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
30
期数:
2006年第3期
页码:
168-172
栏目:
放射生物学
出版日期:
1900-01-01

文章信息/Info

Title:
Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy on pancreatic cancer
作者:
刘军叶;  郭鹞;  郭国祯
710032 西安, 第四军医大学军事预防医学系放射医学教研室
Author(s):
LIU Jun-ye;  GUO Yao;  GUO Guo-zhen
Department of Radiation Medicine, Fourth Military Medical University, Xi’an 710032, China
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
Keywords:
Cell hypoxia; Pancreatic neoplasms; Gene expression regulation; neoplastic; Cytosine deaminase; Radiotherapy
分类号:
R730.54
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。
Abstract:
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-5HRE/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-BCD/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.

参考文献/References:

1 Duffy JP, Eibl G, Reber HA, et al. Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer. Mol Cancer,2003, 22(1):2-12.
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4 Shi Y, Zhai H, Fan D, et al. Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis. Exp Cell Res, 2004, 296(2):337-346.
5 Smythe WR. Prodrug/drug sensitivity gene therapy:current status.Curr Oncol Rep, 2000, 2(1):17-22.
6 Liu J, Zou WG, Liu XY, et al. Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter. Int J Oncol, 2002, 21(3):661-666.
7 Zhang SN. Yuan SZ, Zeng ZY, et al. Apoptosis induced by 5-flucytosine in human pancreatic cancer cells genetically modified to express cytosine deaminase. Acta Pharmacol Sin, 2000, 21(7):655-659.
8 Pan X, Li ZS, Tu ZX, et al. Adenovirus-mediated gene transfer in the treatment of pancreatic cancer. Pancreas, 2003, 26(3):274-278.
9 Chadderton N, Cowen RL, Williams KJ, et al. Dual responsive promoters to target therapeutic gene expression to radiation-resistant hypoxic tumor cells. Int J Radiat Oncol Biol Phys, 2005,62(1):213-222.
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备注/Memo

备注/Memo:
收稿日期:2006-01-09。
通讯作者:郭国祯(E-mail:guozhengg@hotmail.com)
更新日期/Last Update: 1900-01-01