中华放射医学与防护杂志

秦阳华,杨剑,王春刚,等.FHIT基因转染增强人肝癌细胞HepG₂辐射敏感性[J].中华放射医学与防护杂志,2007,27(6):521-527.YANG Jian,YANG Jian,WANG Chun-gang,et al.Transfection of FHIT gene enhances the radiosensitivity of the human hepatocellular carcinoma cell line Hep G₂[J].Chin J Radiol Med Prot,2007,27(6):521-527

FHIT基因转染增强人肝癌细胞HepG₂辐射敏感性

Transfection of FHIT gene enhances the radiosensitivity of the human hepatocellular carcinoma cell line Hep G₂

投稿时间：2006-11-20

DOI：

中文关键词: 电离辐射脆性组胺酸三联体基因治疗

英文关键词:Ionizing radiation Fragile histidine triad Gene therapy

基金项目:国家自然科学基金资助项目(10575130)

作者	单位	E-mail
秦阳华	200433 上海, 第二军医大学海医系放射医学教研室
杨剑	200433 上海, 第二军医大学海医系放射医学教研室
王春刚	200433 上海, 第二军医大学海医系放射医学教研室
高娴	200433 上海, 第二军医大学海医系放射医学教研室
肖瑶	200433 上海, 第二军医大学海医系放射医学教研室
韩玲	200433 上海, 第二军医大学海医系放射医学教研室	linghan8888@yahoo.com.cn

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中文摘要:

目的探讨脆性组胺酸三联体基因转染对肿瘤细胞辐射敏感性的影响。方法首先构建了含有FHIT基因编码序列的真核表达质粒pcDNA/FHIT,并转染人肝癌细胞株Hep G2得到表达正常FHIT蛋白的细胞株Hep G₂/FHIT。然后利用CCK-8和流式细胞仪等方法研究了Hep G₂/FHIT细胞接受 ⁶⁰Co γ射线电离辐射后细胞周期、增殖和凋亡的改变。结果研究表明人肝癌细胞Hep G₂重新表达FHIT后其对电离辐射的敏感性增加,表现为接受电离辐射后细胞存活率下降,凋亡细胞增加。细胞周期检测发现Hep G₂重新表达FHIT后接受电离辐射后发生G₂期阻滞的程度减轻。结论 FHIT基因缺失的肿瘤细胞重新表达正常的FHIT蛋白可以提高其辐射敏感性,并且辐射敏感性提高可能是和FHIT基因抑制了ATR/CHK 1通路活性有关。FHIT基因-电离辐射联合治疗肿瘤,具有一定的协同作用,可以作为一个较好的肿瘤基因治疗的靶点。

英文摘要:

Objective To evaluate the potential of the combination of fragile histidine triad (FHIT) gene therapy and radiation treatment.Methods A plasmid (pcDNA/FHIT) containing an open reading frame of FHIT gene was estabilished,and then the plasmid was transfected into a human hepatocellular carcinoma cell line (Hep G₂). Using G418 for selection, a cell line (Hep G_-2/FHIT) was generated which stably expressing FHIT gene. Using cell counting kit_8 and flow cytometry,the survival fraction, cell cycle and apoptosis of the Hep G_-2/FHIT cells after exposure to ⁶⁰Co γ-ray were measured.Results The transfection of FHIT gene enhanced the radiosensitivity of the Hep G_-2 cell. The Hep G_-2 cells without FHIT showed stronger G_-2 checkpoint response, which indicated that enhanced radiosensitivity was due to the FHIT gene's role in the ATR/CHK 1 pathway.Conclusions Combining γ-rays with FHIT transfection might be an effective way to treat the radioresistant cancer and FHIT might be a potential gene target for tumor treatment.

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