Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer.
Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer.
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DOI：
10.3748/wjg.v10.i3.400
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发表时间：
2004-02
影响因子：
4.3
通讯作者：
Jing Wang;Xiao-xuan Lu;Dao-zhen Chen;Shufeng Li;Li-shan Zhang
中科院分区：
文献类型：
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作者：
Jing Wang;Xiao-xuan Lu;Dao-zhen Chen;Shufeng Li;Li-shan Zhang
目的探讨单纯疱疹病毒胸苷激酶基因（HSV-TK）自杀基因治疗系统联合核苷酸类似物更昔洛韦（GCV）对人胰腺癌的体外治疗作用，为胰腺癌的临床治疗提供新的方法。方法用复制缺陷型逆转录病毒载体GINaTK（含HSV TK基因）使包装细胞PA 317产生子代病毒粒子。然后将HSV-TK基因转染到靶细胞SW 1990中，用GCV处理这些基因修饰的肿瘤细胞，用MTT法研究细胞对GCV的敏感性及其旁观者效应。结果成功构建了包装细胞PA 317/TK，并通过病毒子代感染获得了SW 1990/TK。基因修饰的胰腺癌细胞对GCV的敏感性明显高于未修饰的胰腺癌细胞（t=4.15，n=10，P<0.0025）。将两种细胞按不同比例混合后，观察到明显的旁观者效应。结论HSV-TK/GCV自杀基因治疗系统对胰腺癌有较好的治疗效果，是一种潜在的胰腺癌治疗方法。
AIM To investigate the in vitro effects of suicide gene therapy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer. METHODS We used a replication defective recombinant retrovirus vector GINaTK (bearing HSV-TK gene) to make packaging cell PA317 produce progeny virions. We then transferred the HSV-TK gene to target cells SW1990 using these progeny virions, and treated these gene-modified tumor cells with GCV to study the sensitivity of the cells to GCV and their bystander effects by routine MTT-method. RESULTS Packaging cell PA317/TK was successfully constructed, and we acquired SW1990/TK through virus progeny infection. These gene-modified pancreatic cancer cells were sensitive to the treatment of GCV compared with unmodified tumor cells (t=4.15, n=10, P<0.0025). We also observed a remarkable bystander effect by mixing two kinds of cells at different ratio. CONCLUSION Our data demonstrate that HSV-TK/GCV suicide gene therapy system is effective for treating experimental human pancreatic cancer, which is largely resistant to the common therapies, so the suicide gene therapy system may be a potential treatment approach for pancreatic cancer.