CacyBP/SIP inhibits Doxourbicin-induced apoptosis of glioma cells due to activation of ERK1/2

IUBMB Life. 2016 Mar;68(3):211-9. doi: 10.1002/iub.1477. Epub 2016 Jan 30.

Abstract

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) was previously reported to promote the proliferation of glioma cells. However, the effect of CacyBP/SIP on apoptosis of glioma is poorly understood. Here, our study shows that CacyBP/SIP plays a role in inhibiting doxorubicin (DOX) induced apoptosis of glioma cells U251 and U87. Overexpression of CacyBP/SIP obviously suppressed the DOX-induced cell apoptosis. On the contrary, silencing of CacyBP/SIP significantly promoted it. Further investigation indicated that inhibition of apoptosis by CacyBP/SIP was relevant to its nuclear translocation in response to the DOX treatment. Importantly, we found that the level of p-ERK1/2 in nuclei was related to the nuclear accumulation of CacyBP/SIP. Finally, the role of CacyBP/SIP was confirmed in vivo in a mouse model with the cell line stably silencing CacyBP/SIP. Taken together, our results suggest that CacyBP/SIP plays an important role in inhibiting apoptosis of glioma cells which might be mediated by ERK1/2 signaling pathway, which will provide some guidance for the treatment of glioma.

Keywords: CacyBP/SIP; ERK1/2; apoptosis; chemotherapy; glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Calcium-Binding Proteins / physiology*
  • Cell Line, Tumor
  • Cell Nucleus / enzymology
  • Disease Progression
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • MAP Kinase Signaling System*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Tumor Burden
  • Up-Regulation / drug effects

Substances

  • Antibiotics, Antineoplastic
  • CACYBP protein, human
  • Calcium-Binding Proteins
  • Doxorubicin