Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference
Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference
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DOI：
10.1038/sj.gt.3302391
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发表时间：
2005-01-01
期刊：
影响因子：
5.1
通讯作者：
Kawakami, Y
中科院分区：
文献类型：
--
作者：
Sumimoto, H;Yamagata, S;Kawakami, Y
Skp-2的增加参与细胞周期调节因子包括p27（Kip 1）、p21和c-myc的降解，是各种癌症中细胞周期失调的重要机制之一。我们应用RNA干扰（RNAi）Skp-2通过使用HIV-慢病毒或腺病毒载体的人小细胞肺癌细胞系与增加Skp-2，以评估癌症基因治疗的RNAi策略。HIV-慢病毒介导的针对Skp-2的RNAi通过增加p27（Kip 1）和p21而有效抑制Skp-2增加的癌细胞的体外细胞生长，但对Skp-2不高表达的细胞的生长没有显著影响。此外，瘤内施用Skp-2的腺病毒siRNA载体有效地抑制了NOD/SCID小鼠上建立的皮下肿瘤的生长。这些结果表明，Skp-2 RNAi可能是一个有用的策略，为基因治疗的癌症与高Skp-2表达。
Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27(Kip1), p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27(Kip1) and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.