Down-regulation of ABCE1 inhibits temozolomide resistance in glioma through the PI3K/Akt/NF-κB signaling pathway

Biosci Rep. 2018 Dec 11;38(6):BSR20181711. doi: 10.1042/BSR20181711. Print 2018 Dec 21.

Abstract

The ATP binding cassette (ABC) E1 (ABCE1), a member of the ABC family, was originally described as the RNase L inhibitor. Through forming a heterodimer with RNase L, ABCE1 participates in the negative regulation of the 2-5A/RNase L system and thus mediates a wide range of biological functions. Recent evidence has shown the new roles of ABCE1 in tumorigenesis. However, there have been no investigations on the specific effect of ABCE1 on glioma. In the present study, we examined the expression pattern and possible role of ABCE1 in glioma. Our study demonstrated that ABCE1 was up-regulated in glioma tissues and cell lines. Down-regulation of ABCE1 inhibited temozolomide (TMZ) resistance of glioma cells in vitro and in vivo In addition, we found that the PI3K/Akt/NF-κB pathway was involved in ABCE1-mediated chemoresistance of glioma cells. Taken together, our study suggested ABCE1 as a promising target for glioma chemotherapy.

Keywords: ATP binding cassette E1 (ABCE1); PI3K/Akt/NF-κB signaling pathway; glioma; temozolomide (TMZ) resistance.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Down-Regulation*
  • Drug Resistance, Neoplasm*
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / metabolism
  • Humans
  • Male
  • Mice, Nude
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Signal Transduction / drug effects
  • Temozolomide / pharmacology*
  • Temozolomide / therapeutic use

Substances

  • ABCE1 protein, human
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents, Alkylating
  • NF-kappa B
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Temozolomide