Small interfering RNA targeting of Recepteur d'Origine Nantais induces apoptosis via modulation of nuclear factor-κB and Bcl-2 family in gastric cancer cells

  • Authors:
    • Jung Sun Park
    • Ji Hye Park
    • Soong Lee
    • Young Eun Joo
    • Young Do Jung
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/or_00000911
  • Pages: 709-714
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Abstract

The abnormal accumulation and activation of the receptor tyrosine kinase, Recepteur d'Origine Nantais (RON), has been implicated in tumorigenesis and metastasis in epithelial tumors including gastric cancer. This study examined whether the sequence-specific small interfering RNA (siRNA) suppression of the RON expression could induce apoptotic cell death, and investigated the involved molecular mechanisms. Sequence-specific siRNA effectively suppressed the RON expression at both the mRNA and protein levels. Silencing of the RON expression significantly inhibited gastric cancer cell proliferation and induced apoptosis in a time-dependent manner. The induction of apoptosis was confirmed by the ladder-patterned DNA fragmentation, the presence of cleaved and condensed nuclear chromatin and the increased number of annexin V-positive cells. RON-targeted siRNA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation as revealed by an altered electrophoretic mobility shift. In agreement with this, silencing of the RON expression resulted in a decrease in the nuclear level of the p65 subunit of NF-κB. The transfection of siRNA, which blocked the RON expression, also caused a change in the ratio of Bax/Bcl-2 in a manner that favored apoptosis. The siRNA silencing of RON induced cytochrome c release and the activation of caspase-8 and caspase-9. These results indicate that RON-targeted siRNA could be therapeutically efficacious by inducing cell apoptosis through the modulation of the NF-κB and Bcl-2 family in gastric cancer cells.

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September 2010
Volume 24 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Park JS, Park JH, Lee S, Joo YE and Jung YD: Small interfering RNA targeting of Recepteur d'Origine Nantais induces apoptosis via modulation of nuclear factor-κB and Bcl-2 family in gastric cancer cells . Oncol Rep 24: 709-714, 2010
APA
Park, J.S., Park, J.H., Lee, S., Joo, Y.E., & Jung, Y.D. (2010). Small interfering RNA targeting of Recepteur d'Origine Nantais induces apoptosis via modulation of nuclear factor-κB and Bcl-2 family in gastric cancer cells . Oncology Reports, 24, 709-714. https://doi.org/10.3892/or_00000911
MLA
Park, J. S., Park, J. H., Lee, S., Joo, Y. E., Jung, Y. D."Small interfering RNA targeting of Recepteur d'Origine Nantais induces apoptosis via modulation of nuclear factor-κB and Bcl-2 family in gastric cancer cells ". Oncology Reports 24.3 (2010): 709-714.
Chicago
Park, J. S., Park, J. H., Lee, S., Joo, Y. E., Jung, Y. D."Small interfering RNA targeting of Recepteur d'Origine Nantais induces apoptosis via modulation of nuclear factor-κB and Bcl-2 family in gastric cancer cells ". Oncology Reports 24, no. 3 (2010): 709-714. https://doi.org/10.3892/or_00000911