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首页> 外文期刊>Gene Therapy and Molecular Biology >ets-1 mRNA as target for antisense radio- oligonucleotide therapy in melanoma cells
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ets-1 mRNA as target for antisense radio- oligonucleotide therapy in melanoma cells

机译：ets-1 mRNA作为黑色素瘤细胞反义放射寡核苷酸治疗的靶标

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Angiogenesis provides a novel target for anticancer therapy, in particular radiochemo-therapy as endothelial cells in the vascular wall are sensitive to radiation. Antisense phosphorothioate oligodeoxynucleotides (AS-PODNs) may serve as vehicles for carrying cytotoxic or radioactive agents into a particular intracellular location. Radiolabelled AS-PODNs have the potential of having both antisense and radiation effects. Recently, vascular endothelial growth factor (VEGF)-induced invasiveness was shown to be specifically inhibited by AS-PODN directed against ets-1. Previous studies have shown that radio-oligonucleotide therapy may be effective with AS-PODNs internally labelled with 32P, 33P or35S. Theoretically, 35S gave the smallest variation in nuclear dose in the different cell dimensions studied (Kairemo et al., Cancer Gene Ther 1998; 5: 408-12). This means that cell nuclear targets should be treated with the short range β-emitters 35S or 33P for optimal radio-oligonucleotide therapy. Here we explore this possibility using 33P labeled 17-mer AS-PODNs directed against ets-1 in human melanoma cells in vitro. Inhibition of cell growth was observed in the following order: labeled AS-PODN > nonlabeled AS-PODN > labeled sense PODN > nonlabeled sense PODN > transfection agent. Even with a single 33P at the 5 ?-end of the AS- PODN melanoma cell uptake of label was approximately 0.5 mBq/cell. The nuclear doses in this experiment varied from 1.9 to 3.7 cGy. Thus, in vitro and in vivo use of radio-oligonucleotide therapy utilizing 33P radionanotargeting, e.g. in angiogenesis through ets-1, are highly recommended.
机译：血管生成为抗癌治疗提供了新的靶标，尤其是放射化学治疗，因为血管壁中的内皮细胞对放射线敏感。反义硫代磷酸酯寡聚脱氧核苷酸（AS-PODN）可用作将细胞毒性或放射性试剂携带到特定细胞内位置的载体。放射性标记的AS-PODN具有反义和辐射作用的潜力。最近，血管内皮生长因子（VEGF）诱导的侵袭性已被针对ets-1的AS-PODN特异性抑制。先前的研究表明，放射-寡核苷酸疗法可能对内部标记有32P，33P或35S的AS-PODN有效。从理论上讲，在研究的不同细胞尺寸中，35S产生的核剂量变化最小（Kairemo等，Cancer Gene Ther 1998; 5：408-12）。这意味着细胞核靶标应使用短距离β-发射子35S或33P治疗，以实现最佳的放射性寡核苷酸治疗。在这里，我们探讨了使用33P标记的17-mer AS-PODNs在人黑素瘤细胞中针对ets-1的可能性。以下列顺序观察到细胞生长的抑制：标记的AS-PODN>未标记的AS-PODN>标记的有义PODN>未标记的有义PODN>转染剂。即使在AS-PODN黑色素瘤的5β端只有一个33P，细胞对标记的摄取仍约为0.5 mBq /细胞。在该实验中的核剂量在1.9至3.7cGy之间变化。因此，在体外和体内利用放射性寡核苷酸疗法利用33P放射性纳米靶向，如高度推荐通过ets-1进行血管生成。

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