RNAse A-like enzymes in serum inhibit the anti-neoplastic activity of siRNA targeting Polo-like kinase 1
RNAse A-like enzymes in serum inhibit the anti-neoplastic activity of siRNA targeting Polo-like kinase 1
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DOI：
10.1002/ijc.22665
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发表时间：
2007-07-01
影响因子：
6.4
通讯作者：
Piiper, Albrecht
中科院分区：
文献类型：
--
作者：
Haupenthal, Joerg;Baehr, Christina;Piiper, Albrecht
通过小干扰 (si) RNA 下调肿瘤细胞中的靶分子是一种有前途的抗癌策略。这种方法的一个主要挑战是 siRNA 体内沉默活性的丧失。我们的研究旨在调查血清区室对针对 Polo 样激酶 I (Plk1)（一种有丝分裂相关丝氨酸/苏氨酸激酶）的 siRNA 抗肿瘤活性的影响。数据显示，siRNA 诱导的 Plk1 表达抑制有效地减少了几种癌细胞系中的活细胞质量并增加了细胞凋亡。在人血清中预孵育 siRNA 会导致 siRNA 缩短，并丧失其 Plk1 沉默和抗肿瘤活性。通过抑制 RNAse A 样酶可以防止这种活性丧失。这些数据表明，siRNA 的抗肿瘤作用在人血清中孵育后会下降。这种抗肿瘤活性的丧失可以通过抑制 RNAse A 样酶的降解来防止。这可能对 siRNA 人类治疗应用的开发具有重要意义。 (C) 2007 Wiley-Liss, Inc.
Down-modulation of target molecules in tumor cells by small interfering (si) RNAs is a promising anti-cancer strategy. A major challenge of this approach is the loss of silencing activity of the siRNAs in vivo. Our study aimed at investigating the influence of the serum compartment on the anti-tumor activity of siRNA directed against Polo-like kinase I (Plk1), a mitosis-associated serine/threonine kinase. The data showed that siRNA-induced suppression of Plk1 expression effectively reduced the viable cell mass and increased apoptosis in several cancer cell lines. Preincubation of the siRNA in human serum led to shortening of the siRNA as well as loss of its Plk1 silencing and anti-tumor activity. This loss of activity was prevented by inhibition of RNAse A-like enzymes. These data indicate that the anti-neoplastic effect of siRNAs declines upon incubation in human serum. This loss of anti-neoplastic activity can be prevented by inhibition of their degradation by RNAse A-like enzymes. This may have important implications for the development of a human therapeutic application of siRNAs. (C) 2007 Wiley-Liss, Inc.