Targeting and eradicating cancer cells by a prostate-specific vector carrying the diphtheria toxin A gene.
Targeting and eradicating cancer cells by a prostate-specific vector carrying the diphtheria toxin A gene.
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通过携带白喉毒素 A 基因的前列腺特异性载体靶向并根除癌细胞。
DOI：
10.1038/sj.cgt.7700197
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Pang,S
中科院分区：
文献类型：
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作者：
Pang,S
前列腺癌是美国男性最常见的恶性肿瘤。开发前列腺癌的基因疗法很重要，因为这种疾病的晚期患者还没有有效的治疗方法。组织特异性启动子转录靶向癌细胞是前列腺癌基因治疗的一种很有前途的方法。我们先前根据前列腺特异性抗原基因的近端启动子和上游调控序列构建了前列腺特异性启动子。在这里描述的实验中，我们修改了我们的前列腺特异性启动子，以驱动白喉毒素基因(DTA)的A结构域在质粒载体中。利用脂质体介导的转染法，可以有效地将该质粒载体导入细胞系。在转染腺癌细胞系LNCaP中，DTA基因被激活转录，并显著抑制蛋白质合成和细胞病变效应。而对照细胞系未见明显致病效应。因此，DTA基因载体的高度特异性和高效的细胞病变作用对于转移性前列腺癌患者的全身治疗具有潜在的应用价值。
Prostate cancer is the most commonly diagnosed malignancy in American men. Developing gene therapy for prostate cancer is important, because there is no effective treatment for patients in the advanced stages of this disease. A tissue-specific promoter to transcriptionally target cancer cells is a promising approach for gene therapy of prostate cancer. We previously constructed a prostate tissue-specific promoter based on the proximal promoter and the upstream regulatory sequence of the prostate-specific antigen gene. In the experiments described here, we modified our prostate-specific promoter to drive the A domain of the diphtheria toxin gene (DTA) in a plasmid vector. The plasmid vector can be efficiently transfected into cell lines, using a liposome-mediated transfection method. In the transfected prostate cell line, LNCaP, the DTA gene was actively transcribed, and significant inhibition of protein synthesis and cytopathic effects was observed. However, no pathogenic effects were apparent in the control cell lines. The highly specific and efficient cytopathicity of the DTA gene vector is therefore potentially useful for systemic treatment of patients with metastatic prostate cancer.