Melanoma differentiation associated gene-7 (mda-7): A novel anti-tumor gene for cancer gene therapy
Melanoma differentiation associated gene-7 (mda-7): A novel anti-tumor gene for cancer gene therapy
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DOI：
10.1007/bf03401847
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发表时间：
2001-04-01
影响因子：
5.7
通讯作者：
Chada, S
中科院分区：
文献类型：
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作者：
Mhashilkar, AM;Schrock, RD;Chada, S
背景：MDA-7基因(黑色素瘤分化相关基因-7)是一种新的肿瘤抑制基因。丙二醛-7的抗增殖活性已有报道。在本报告中，我们分析了Ad-MDA7在广泛的肿瘤细胞系中的抗肿瘤效果。材料和方法：检测转导Ad-MDA7的癌细胞和正常细胞系的细胞增殖(氚胸苷掺入法)。结果：Ad-MDA7对肿瘤细胞的生长抑制和凋亡诱导作用呈时间和剂量依赖性。其抗肿瘤作用与这些细胞中p53、RE、p16、ras、bar和caspase3的基因组状态无关。此外，正常细胞株对Ad-MDA7没有表现出增殖抑制或凋亡反应。此外，转导Ad-MDA7的癌细胞分泌一种可溶形式的MDA-7蛋白。结论：Ad-MDA7在肿瘤细胞中具有较强的选择性杀伤活性，而在正常细胞中不具有杀伤活性，是一种潜在的肿瘤基因治疗载体。
Background: The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines.Materials and Methods: Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay. Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis).Results: Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RE, p16, ras, bar, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers.Conclusions: The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.