Knockdown of retinoblastoma protein may sensitize glioma cells to cisplatin through inhibition of autophagy

Neurosci Lett. 2016 May 4:620:137-42. doi: 10.1016/j.neulet.2016.04.001. Epub 2016 Apr 2.

Abstract

Glioblastoma multiforme (GBM) is one of the deadliest forms of cancer due to its limited sensitivity to chemotherapy and radiotherapy. Cisplatin (CCDP) is a widely used chemotherapeutic agent for tumors, but the agent often results in the development of chemo-resistance. In several cancers, cisplatin resistance is associated with autophagy induction. Here, we found that in glioma cells cisplatin treatment induced autophagy. Our data indicates that the autophagy induction plays a critical role in cisplatin resistance of glioma cells, knockdown of RB inhibited autophagy induced by cisplatin, and inhibition of autophagy improved cisplatin-induced apoptosis. It suggests that a combination of autophagy inhibitors with cisplatin may improve the therapeutic efficiency of cisplatin towards GBM with acquired resistance.

Keywords: Apoptosis; Autophagy; Cisplatin; Glioblastoma; Retinoblastoma protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Autophagy / drug effects*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Gene Knockdown Techniques
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Retinoblastoma Protein / genetics*

Substances

  • Antineoplastic Agents
  • RNA, Small Interfering
  • Retinoblastoma Protein
  • Cisplatin