Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo

Int J Nanomedicine. 2012;7:3659-66. doi: 10.2147/IJN.S33584. Epub 2012 Jul 12.

Abstract

Hydroxyapatite nanoparticles (nano-HAPs) have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose- and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

Keywords: glioma; growth mechanism; hydroxyapatite nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cell Shape / drug effects
  • Durapatite / chemistry
  • Durapatite / pharmacology*
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Matrix Attachment Region Binding Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Organic Cation Transport Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-met / metabolism

Substances

  • Antineoplastic Agents
  • Matrix Attachment Region Binding Proteins
  • Organic Cation Transport Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • SATB1 protein, human
  • SLC22A18 protein, human
  • Durapatite
  • Proto-Oncogene Proteins c-met
  • Casp3 protein, mouse
  • Caspase 3