Enhancement of cytarabine sensitivity in squamous cell carcinoma cell line transfected with deoxycytidine kinase
Enhancement of cytarabine sensitivity in squamous cell carcinoma cell line transfected with deoxycytidine kinase
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DOI：
10.1001/archotol.128.6.708
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发表时间：
2002-06-01
影响因子：
--
通讯作者：
Manome, Y
中科院分区：
文献类型：
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作者：
Kojima, H;Iida, M;Manome, Y
背景：阿糖胞苷是目前已知治疗急性髓系白血病最有效的药物。其抗肿瘤作用是通过在复制过程中与DNA结合，然后破坏DNA链来表达的。然而，阿糖胞苷对大多数实体肿瘤只有有限的活性，包括头颈部的鳞状细胞癌。其原因被认为是在实体肿瘤细胞系中，降解阿糖胞苷的酶胞苷脱氨酶的表达量很高，而磷酸化阿糖胞苷（前药）的脱氧胞苷激酶（dCK）的表达量很低。目的：探讨头颈部鳞状细胞癌是否可以通过将平衡从降解途径转变为激活途径而对阿糖胞苷的细胞毒作用更加敏感。方法：用含有DCK基因的逆转录病毒载体或腺病毒载体转染人SCC-25鳞癌细胞，用Northern blot法检测DCK的表达。使用这些细胞进行阿糖胞苷暴露后的体外细胞毒性测定。结果：逆转录病毒和腺病毒载体介导的dCK互补DNA转导导致舌鳞癌细胞对体外阿糖胞苷的细胞毒性作用显着增敏。结论：dck -阿糖胞苷系统可能是头颈部鳞状细胞癌基因治疗的有效途径。
Background: Cytarabine is the most effective agent known for the treatment of acute myeloid leukemia. its antitumor effect is expressed by combining with DNA during replication and then destroying the DNA chain. However, cytarabine has only limited activity against most solid tumors, including squamous cell carcinoma of the head and neck. The reason for this is thought to be that in cell lines of solid tumors the expression of cytidine deaminase, an enzyme that degrades cytarabine, is high, whereas the expression of deoxycytidine kinase (dCK), which phosphorylates cytarabine (a prodrug), is weak.Objective: To determine whether head and neck squamous cell carcinomas can be made more sensitive to the cytotoxic effects of cytarabine by shifting the balance from the degradative to the activation pathway.Methods: Human SCC-25 squamous carcinoma cells were transfected by either retroviral vector or adenoviral vector containing DCK gene and were identified for dCK expression by Northern blot analysis. In vitro cytotoxic assay after cytarabine exposure was performed using these cells.Results: Both retroviral and adenoviral vector-mediated transduction of the dCK complementary DNA resulted in marked sensitization of tongue squamous carcinoma cell lines to the cytotoxic effects of cytarabine in vitro.Conclusion: The dCK-cytarabine system may be a useful approach for gene therapy of squamous cell carcinomas of the head and neck.