High-mobility group protein B1 silencing promotes susceptibility of retinoblastoma cells to chemotherapeutic drugs through downregulating nuclear factor-κB

  • Authors:
    • Yong Chai
    • Juhua Xiao
    • Shouhua Zhang
    • Yunyan Du
    • Zhipeng Luo
    • Xin Zhou
    • Kai Huang
  • View Affiliations

  • Published online on: January 10, 2018     https://doi.org/10.3892/ijmm.2018.3379
  • Pages: 1651-1658
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Abstract

The aim of the present study was to investigate the effects of high-mobility group protein B1 (HMGB1) silencing on the susceptibility of retinoblastoma (RB) cells to chemotherapeutic drugs and the underlying molecular mechanisms. Western blot analysis revealed that vincristine (VCR), etoposide (ETO) and carboplatin (CBP) significantly increased the expression of HMGB1 in Weri‑Rb-1 and Y79 cells compared with the untreated control (P<0.01). siRNA HMGB1 and siRNA negative control (NC) were transfected to Y79 cells by Lipofectamine™ 2000 and, following VCR treatment, the expression of HMGB1 and nuclear factor-κB (NF-κB) was analyzed. siRNA HMGB1 transfection silenced HMGB1 expression. The cytotoxicity of VCR to cells with and without siRNA HMGB1 was investigated by methyl thiazolyl tetrazolium (MTT) assay. siRNA HMGB1 markedly reduced the IC50 value of VCR to RB cells through downregulating the expression of NF-κB, similar to pyrrolidinedithiocarbamate (PDTC). Moreover, following siRNA HMGB1, siRNA NC and ammonium PDTC treatment, the apoptosis of RB cells with VCR incubation was evaluated by Hoechst staining, and the expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), Beclin 1 and p62 were determined with western blot analysis. The LC3 puncta were determined with immunofluorescence assay. The results demonstrated that VCR treatment significantly downregulated the expression of cleaved caspase-3, cleaved PARP and p62, and upregulated the expression of Beclin 1 in RB cells (P<0.01). Similar to the NF-κB inhibitor PDTC, siRNA HMGB1 significantly promoted apoptosis and suppressed autophagy of VCR‑treated RB cells through reversing the effects of VCR on these signaling molecules (P<0.01). Therefore, HMGB1 silencing promoted the susceptibility of RB cells to chemotherapeutic drugs through downregulating NF-κB.
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March 2018
Volume 41 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Chai, Y., Xiao, J., Zhang, S., Du, Y., Luo, Z., Zhou, X., & Huang, K. (2018). High-mobility group protein B1 silencing promotes susceptibility of retinoblastoma cells to chemotherapeutic drugs through downregulating nuclear factor-κB. International Journal of Molecular Medicine, 41, 1651-1658. https://doi.org/10.3892/ijmm.2018.3379
MLA
Chai, Y., Xiao, J., Zhang, S., Du, Y., Luo, Z., Zhou, X., Huang, K."High-mobility group protein B1 silencing promotes susceptibility of retinoblastoma cells to chemotherapeutic drugs through downregulating nuclear factor-κB". International Journal of Molecular Medicine 41.3 (2018): 1651-1658.
Chicago
Chai, Y., Xiao, J., Zhang, S., Du, Y., Luo, Z., Zhou, X., Huang, K."High-mobility group protein B1 silencing promotes susceptibility of retinoblastoma cells to chemotherapeutic drugs through downregulating nuclear factor-κB". International Journal of Molecular Medicine 41, no. 3 (2018): 1651-1658. https://doi.org/10.3892/ijmm.2018.3379