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The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells

  • Authors:
    • Tuanjie Zhao
    • Yingchen Xu
    • Shulin Ren
    • Chaojie Liang
    • Xiaona Zhou
    • Jixiang Wu
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    Affiliations: Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4370-4378
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    Published online on: March 19, 2018
       https://doi.org/10.3892/etm.2018.5964
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Abstract

Dysfunctional Fas ligand (FasL) may inhibit the apoptosis of tumor cells. FasL contains two receptors, Fas and Decoy Receptor 3 (DcR3). DcR3 competitively binds to FasL over Fas, resulting in the inhibition of FasL‑mediated apoptosis. Therefore, it was suggested that the downregulation of DcR3 expression enhances FasL‑mediated apoptosis. In the current study, the expression of DcR3 was silenced in liver cancer HepG2 cells in order to study the effect of FasL on HepG2 cell activity and invasiveness. DcR3 siRNA knockdown HepG2 cells (KD), DcR3 blank plasmid control HepG2 cells and wild‑type HepG2 cells (WT) were treated with FasL (10 ng/ml). Flow cytometry was used to detect changes in the cell cycle and apoptosis. MTS, clonogenic, wound healing and Transwell assays were performed to examine changes in cell activity, proliferation, migration and invasiveness. Reverse transcription polymerase chain reaction and western blot analysis were performed to measure the expression of DcR3, matrix metallopeptidase 9 (MMP9), vascular endothelial growth factor (VEGF)‑C and VEGF‑D. The results demonstrated that, compared with WT cells, the proportion of KD cells in the G2/M phase decreased following treatment with FasL. KD cells were more sensitive to FasL‑induced apoptosis. Following treatment with FasL, the activity and proliferation, migration and invasion of KD cells were reduced, and the expression of MMP9, VEGF‑C and VEGF‑D decreased. Furthermore, it was demonstrated that DcR3 is involved in the proliferation and invasion of HepG2 cells, and this mechanism may be associated with the regulatory effect of the expression of MMP9, VEGF‑C and VEGF‑D; however, the exact mechanism of action remains unclear. FollowingDcR3 silencing, FasL‑mediated apoptosis increased in HepG2 cells. Therefore, DcR3 combined with FasL may be a potential target for the treatment of liver cancer.
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Spandidos Publications style
Zhao T, Xu Y, Ren S, Liang C, Zhou X and Wu J: The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells. Exp Ther Med 15: 4370-4378, 2018.
APA
Zhao, T., Xu, Y., Ren, S., Liang, C., Zhou, X., & Wu, J. (2018). The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells. Experimental and Therapeutic Medicine, 15, 4370-4378. https://doi.org/10.3892/etm.2018.5964
MLA
Zhao, T., Xu, Y., Ren, S., Liang, C., Zhou, X., Wu, J."The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells". Experimental and Therapeutic Medicine 15.5 (2018): 4370-4378.
Chicago
Zhao, T., Xu, Y., Ren, S., Liang, C., Zhou, X., Wu, J."The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells". Experimental and Therapeutic Medicine 15, no. 5 (2018): 4370-4378. https://doi.org/10.3892/etm.2018.5964
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Spandidos Publications style
Zhao T, Xu Y, Ren S, Liang C, Zhou X and Wu J: The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells. Exp Ther Med 15: 4370-4378, 2018.
APA
Zhao, T., Xu, Y., Ren, S., Liang, C., Zhou, X., & Wu, J. (2018). The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells. Experimental and Therapeutic Medicine, 15, 4370-4378. https://doi.org/10.3892/etm.2018.5964
MLA
Zhao, T., Xu, Y., Ren, S., Liang, C., Zhou, X., Wu, J."The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells". Experimental and Therapeutic Medicine 15.5 (2018): 4370-4378.
Chicago
Zhao, T., Xu, Y., Ren, S., Liang, C., Zhou, X., Wu, J."The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells". Experimental and Therapeutic Medicine 15, no. 5 (2018): 4370-4378. https://doi.org/10.3892/etm.2018.5964
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