Cellular pharmacology of P-ethoxy antisense oligonucleotides targeted to Bcl-2 in a follicular lymphoma cell line
Cellular pharmacology of P-ethoxy antisense oligonucleotides targeted to Bcl-2 in a follicular lymphoma cell line
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DOI：
10.1080/1042819031000099733
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发表时间：
2003-09-01
影响因子：
2.6
通讯作者：
Lopez-Berestein, G
中科院分区：
文献类型：
--
作者：
Gutiérrez-Puente, Y;Tari, AM;Lopez-Berestein, G
一个P-乙氧基寡核苷酸（oligo），20个碱基长，特异性的翻译起始位点的人Bcl-2 mRNA，被纳入脂质体，以增加其细胞内的交付。该寡核苷酸选择性抑制Bcl-2蛋白表达，并诱导t（14;18）阳性转化滤泡性淋巴瘤（FL）细胞系的生长抑制。我们研究了较短的脂质体P-乙氧基寡聚物（7、9、11或15 mer）的抑制作用，以确定靶向相同Bcl-2 mRNA的不同寡聚链长度的活性。在12 μ M时，所有的寡核苷酸抑制FL细胞系的生长。我们比较了7聚体寡核苷酸与20聚体寡核苷酸。两种寡核苷酸抑制Bcl-2蛋白表达相似：7-和20-mer分别为66%和60%。两种寡核苷酸的摄取和保留也非常相似。我们的结果表明，Bcl-2抑制活性保持与P-乙氧基反义寡核苷酸范围从7至20个碱基。
A P-ethoxy oligonucleotide (oligo), 20 bases long and specific for the translation initiation site of human Bcl-2 mRNA, was incorporated into liposomes to increase its intracellular delivery. This oligo selectively inhibited Bcl-2 protein expression and induced growth inhibition in t(14;18)-positive transformed follicular lymphoma (FL) cell lines. We studied the inhibitory effects of shorter liposomal P-ethoxy oligos (7, 9, 11 or 15 mer) in order to determine the activity of different oligo chain lengths targeted to the same Bcl-2 mRNA. At 12 muM, all the oligos inhibited the growth of a FL cell line. We compared the 7-mer oligo with the 20-mer oligo. The two oligos inhibited Bcl-2 protein expression similarly: 66% and 60% for the 7- and 20-mer, respectively. The uptake and retention of both oligos were also very similar. Our results indicate that the Bcl-2 inhibitory activity is maintained with P-ethoxy antisense oligos ranging from 7 to 20 bases.