LMP-1 induces survivin expression to inhibit cell apoptosis through the NF-κB and PI3K/Akt signaling pathways in nasal NK/T-cell lymphoma

Oncol Rep. 2015 May;33(5):2253-60. doi: 10.3892/or.2015.3847. Epub 2015 Mar 10.

Abstract

The latent membrane protein-1 (LMP-1) is essential for Epstein-Barr virus (EBV)-induced nasal natural killer/T-cell lymphoma (NKTL). The aim of the present study was to evaluate the role of LMP-1 in NKTL. Two human EBV-positive NKTL cell lines (SNK-6 and SNT-8) were transfected with pcDNA3.1-LMP-1 or LMP-1 siRNA. Compared with the blank control, the cell apoptosis rates were decreased by 10.31 and 12.05% after pcDNA3.1-LMP-1 transfection and increased by 41.48 and 35.63% after lentiviral LMP-1 siRNA infection in the SNK-6 and SNT-8 cells. Survivin expression was induced by LMP-1, and the effect was attenuated by inhibitors of survivin, NF-κB and PI3K/Akt. Reduction in cell apoptosis by LMP-1 was also inhibited by inhibitors of survivin, NF-κB and PI3K/Akt. For the in vivo assay, tumor-bearing mice were established by subcutaneous injection with differentially treated SNT-8 cells into the back of the nude mice, and the tumor growth in the different groups was recorded. The results revealed that tumor formation and growth were also inhibited by treatment with survivin, NF-κB and PI3K/Akt inhibitors. Collectively, LMP-1-induced survivin expression inhibited cell apoptosis through the NF-κB and PI3K/Akt pathways, and survivin may be a new target for the treatment of NKTL induced by EBV.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis / physiology
  • Blotting, Western
  • Cell Line, Tumor
  • Cytoskeletal Proteins / metabolism*
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / physiology*
  • Heterografts
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • LIM Domain Proteins / metabolism*
  • Lymphoma, Extranodal NK-T-Cell / metabolism
  • Lymphoma, Extranodal NK-T-Cell / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / metabolism
  • Nose Neoplasms / metabolism
  • Nose Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Survivin
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC5 protein, human
  • Cytoskeletal Proteins
  • Inhibitor of Apoptosis Proteins
  • LIM Domain Proteins
  • NF-kappa B
  • PDLIM7 protein, human
  • Survivin
  • Proto-Oncogene Proteins c-akt