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无针喷射抗 C7orf24 siRNA 抑制肿瘤生长

Prevention of tumor growth by needle-free jet injection of anti-C7orf24 siRNA.

机构信息

Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Japan.

出版信息

Cancer Gene Ther. 2012 Aug;19(8):553-7. doi: 10.1038/cgt.2012.31. Epub 2012 Jun 1.

Abstract

Chromosome 7 open reading frame 24 (C7orf24), which was identified by proteome analysis, is upregulated in various types of cancer and is associated with cellular proliferation. However, in vivo antitumor effect by knockdown of C7orf24 has not been clarified. In this study, we investigated that the antitumor effect of anti-C7orf24 small interfering RNA (siRNA) administered by needle-free jet injection (JI) on lung cancer-bearing mice. Transfection of anti-C7orf24 siRNA induced cytotoxicity in cultured human lung cancer cells through specific knockdown of C7orf24. Furthermore, JI could effectively deliver anti-C7orf24 siRNA to tumor tissues, and as a result tumor growth was significantly inhibited. Immunohistochemical analysis revealed that C7orf24 levels were significantly reduced within tumor tissues collected from anti-C7orf24 siRNA-administered mice, indicating that the knockdown of C7orf24 induced cytotoxicity in tumor tissue. In conclusion, these data show for the first time that knockdown of C7orf24 prevents tumor growth in vivo following JI-mediated the siRNA delivery.

摘要

染色体 7 开放阅读框 24(C7orf24)是通过蛋白质组分析鉴定的,在多种类型的癌症中上调,与细胞增殖有关。然而,通过敲低 C7orf24 对体内肿瘤的抗肿瘤作用尚未阐明。在这项研究中,我们研究了通过无针射流注射(JI)给药的抗 C7orf24 小干扰 RNA(siRNA)对肺癌荷瘤小鼠的抗肿瘤作用。抗 C7orf24 siRNA 的转染通过特异性敲低 C7orf24 诱导培养的人肺癌细胞的细胞毒性。此外,JI 可以有效地将抗 C7orf24 siRNA 递送到肿瘤组织,结果肿瘤生长明显受到抑制。免疫组织化学分析显示,从接受抗 C7orf24 siRNA 治疗的小鼠的肿瘤组织中收集的 C7orf24 水平显著降低,表明 C7orf24 的敲低诱导了肿瘤组织中的细胞毒性。总之,这些数据首次表明,JI 介导的 siRNA 递送后,敲低 C7orf24 可防止体内肿瘤生长。

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