Asymmetric siRNA targeting the bcl‑2 gene inhibits the proliferation of cancer cells in vitro and in vivo

  • Authors:
    • Yan Yin
    • Xu Chen
    • Chang‑Dong Zhang
    • Pei‑Feng Liu
    • You‑Rong Duan
    • Yan‑Rong Fan
    • Zhi‑Wei Wu
    • Geng‑Feng Fu
    • Jian‑Jun Wang
    • Gen‑Xing Xu
  • View Affiliations

  • Published online on: November 7, 2012     https://doi.org/10.3892/ijo.2012.1691
  • Pages: 253-260
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Abstract

Small interfering RNAs (siRNAs) are valuable reagents for efficient gene silencing in a sequence‑specific manner via the RNA interference (RNAi) pathway. The current synthetic siRNA structure consists of symmetrical duplexes of 19‑21 base pairs (bp) with 2 nucleotide (nt) 3' overhangs. In this study, we report that an asymmetric siRNA (asiRNA) consisting of 17 bp duplex region (17 bp asiRNA) exhibited potent activity in inhibiting bcl-2 gene expression and cancer cell proliferation in vitro. Importantly, this asiRNA structure significantly reduced off‑target silencing by the sense strand. To improve the stability of the 17 bp asiRNA, we synthesized a series of chemically modified 17 bp asiRNAs. Further experiments showed that in comparison with the 17 bp asiRNA, the 17 bp asiRNA‑M2, one of the modified 17 bp asiRNAs, exhibited a comparable gene silencing activity and an improved stability in vitro. Furthermore, the 17 bp asiRNA‑M2 with a proteolipid micelle delivery system can effectively suppress the growth of H22 and BGC 803 tumors in vivo. These results suggest that the chemically modified asiRNAs may have potential as an effective therapeutic approach for cancer gene therapy in the future.

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January 2013
Volume 42 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Yin, Y., Chen, X., Zhang, C., Liu, P., Duan, Y., Fan, Y. ... Xu, G. (2013). Asymmetric siRNA targeting the bcl‑2 gene inhibits the proliferation of cancer cells in vitro and in vivo. International Journal of Oncology, 42, 253-260. https://doi.org/10.3892/ijo.2012.1691
MLA
Yin, Y., Chen, X., Zhang, C., Liu, P., Duan, Y., Fan, Y., Wu, Z., Fu, G., Wang, J., Xu, G."Asymmetric siRNA targeting the bcl‑2 gene inhibits the proliferation of cancer cells in vitro and in vivo". International Journal of Oncology 42.1 (2013): 253-260.
Chicago
Yin, Y., Chen, X., Zhang, C., Liu, P., Duan, Y., Fan, Y., Wu, Z., Fu, G., Wang, J., Xu, G."Asymmetric siRNA targeting the bcl‑2 gene inhibits the proliferation of cancer cells in vitro and in vivo". International Journal of Oncology 42, no. 1 (2013): 253-260. https://doi.org/10.3892/ijo.2012.1691