Hasegawa Y, Emi N, Shimokata K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
J Mol Med (Berl). 1995 Mar;73(3):107-12. doi: 10.1007/BF00198237.
We used a recombinant retrovirus as one of the potential vectors for human gene therapy to transfer a drug sensitivity gene into human lung cancer cells. The gene encoding the thymidine kinase (TK) of herpes simplex virus type 1 (HSV1) was used as the drug sensitivity gene. The antiherpes drugs acyclovir (ACV) and ganciclovir (GCV) were chosen to test the HSV1-TK activity transferred into the human lung cancer cell lines. The rationale for this approach was that ACV and GCV are nucleoside analogs specifically converted by HSV1-TK to a toxic form capable of inhibiting DNA synthesis or disrupting cellular DNA replication. The results obtained from our experiments demonstrate that the retroviral vector-mediated HSV1-TK gene transfer leads to ACV- and GCV-dependent cytotoxicity in human lung cancer cell lines, including both small-cell carcinoma and non-small-cell carcinoma. Although the gene transfer of HSV1-TK gene into tumor cells would be one model for gene therapy to control lung cancer, further investigations are necessary for the proper choice of the therapeutic gene and vector targeting such as tumor cell specific delivery of the gene or tumor cell specific expression of the transduced gene.
我们使用重组逆转录病毒作为人类基因治疗的潜在载体之一，将药物敏感性基因导入人肺癌细胞。编码单纯疱疹病毒1型（HSV1）胸苷激酶（TK）的基因被用作药物敏感性基因。选择抗疱疹药物阿昔洛韦（ACV）和更昔洛韦（GCV）来检测导入人肺癌细胞系的HSV1-TK活性。这种方法的基本原理是，ACV和GCV是核苷类似物，可被HSV1-TK特异性转化为能够抑制DNA合成或破坏细胞DNA复制的毒性形式。我们实验获得的结果表明，逆转录病毒载体介导的HSV1-TK基因转移导致人肺癌细胞系（包括小细胞癌和非小细胞癌）中出现ACV和GCV依赖性细胞毒性。尽管将HSV1-TK基因导入肿瘤细胞将是控制肺癌基因治疗的一种模式，但对于治疗基因和载体靶向的正确选择，如基因的肿瘤细胞特异性递送或转导基因的肿瘤细胞特异性表达，仍需要进一步研究。
