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首页> 外文期刊>Journal of International Medical Research >Radiosensitization and Anti-tumour Effects of Cytosine Deaminase and Thymidine Kinase Fusion Suicide Gene in Human Adenoid Cystic Carcinoma Cells
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Radiosensitization and Anti-tumour Effects of Cytosine Deaminase and Thymidine Kinase Fusion Suicide Gene in Human Adenoid Cystic Carcinoma Cells

机译：胞嘧啶脱氨酶和胸苷激酶融合自杀基因在人腺样囊性癌细胞中的放射增敏作用和抗肿瘤作用

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摘要

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) can convert innocuous prodrugs into cytotoxic metabolites and are being investigated for use in gene therapy for cancer. Human adenoid cystic carcinoma (ACC-2) cells transduced with a CD/HSV-TK fusion gene (ACC-2/CD-TK cells) were found to be more sensitive to radiation than ACC-2 cells when exposed to 5-fluorocytosine (5-FC; 40 μg/ml) plus ganciclovir (0.1 μg/ml) for 48 h before irradiation. Analysis of radiation survival curves for cells exposed to 5-FC plus ganciclovir before irradiation showed that ACC-2 cells had a higher capacity for sublethal damage repair (Dq value) and greater cellular radiosensitivity (D0 value) than ACC-2/CD-TK cells. Colony formation rate after 2 Gy of irradiation was significantly greater for ACC-2 than for ACC-2/CD-TK cells when cells were treated with 5-FC plus ganciclovir before irradiation. This study, therefore, indicates that addition of radiation might substantially improve the therapeutic potential of CD-TK fusion gene therapy of human adenoid cystic carcinomas.
机译：单纯疱疹病毒胸苷激酶（HSV-TK）和大肠杆菌胞嘧啶脱氨酶（CD）可以将无害的前药转化为细胞毒性代谢产物，并正在研究用于癌症的基因治疗。发现通过CD / HSV-TK融合基因转导的人类腺样囊性癌（ACC-2）细胞（ACC-2 / CD-TK细胞）在暴露于5-氟胞嘧啶后比ACC-2细胞对辐射更敏感（ 5-FC; 40μg/ ml）加更昔洛韦（0.1μg/ ml）照射48小时。辐照前暴露于5-FC和更昔洛韦的细胞的放射存活曲线分析表明，与ACC-2 / CD-TK相比，ACC-2细胞具有更高的亚致死损伤修复能力（Dq值）和更高的细胞放射敏感性（D0值）。细胞。当在照射前用5-FC +更昔洛韦处理细胞时，ACC-2照射2 Gy后的集落形成率显着高于ACC-2 / CD-TK细胞。因此，这项研究表明，增加放射线可能会大大改善CD-TK融合基因治疗人腺样囊性癌的治疗潜力。

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