Inhibition of glioma growth by a GOLPH3 siRNA-loaded cationic liposomes

J Neurooncol. 2018 Nov;140(2):249-260. doi: 10.1007/s11060-018-2966-6. Epub 2018 Aug 13.

Abstract

Purpose: GOLPH3 has been shown to be involved in glioma proliferation. In this study, we aimed to demonstrate that GOLPH3 can serve as a target for glioma gene therapy.

Methods: During the experiment, cationic liposomes with angiopep-2 (A2-CL) were used to deliver siGOLPH3 crossing the blood-brain barrier and reaching the glioma.

Results: At the cellular level, the A2-CL/siGOLPH3 could silence GOLPH3 and then effectively inhibited the proliferation of cells. In vivo experiments, using U87-GFP-Luci-bearing BALB/c mouse models, we demonstrated that A2-CL could deliver GOLPH3-siRNA specifically to glioma and effectively inhibit glioma growth.

Conclusions: This study shows that GOLPH3 has great potential as a target for the gene therapy of glioma and is of great value in precise medical applications.

Keywords: Angiopep-2; GOLPH3; Glioma; Liposome; RNAi.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cations / chemistry
  • Cations / pharmacokinetics
  • Cations / therapeutic use
  • Cell Line
  • Genetic Therapy*
  • Glioma / diagnostic imaging
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Liposomes / chemistry
  • Liposomes / pharmacokinetics
  • Liposomes / therapeutic use*
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / pharmacokinetics

Substances

  • Cations
  • GOLPH3 protein, human
  • Liposomes
  • Membrane Proteins
  • RNA, Small Interfering