In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles

World J Gastroenterol. 2009 Apr 28;15(16):1966-72. doi: 10.3748/wjg.15.1966.

Abstract

Aim: To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.

Methods: HepG2 cell proliferation was analyzed in vitro using the 3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt assay. The in vivo activity of nanoparticles delivering the MK-ASODNs was analyzed by histopathological and immunohistochemical staining and quantitative real time polymerase chain reaction (PCR).

Results: The in vitro proliferation of HepG2 cells was significantly inhibited by the nanoparticles packaged with MK-ASODNs (NANO-ASODNs). Furthermore, the NANO-ASODNs significantly inhibited the growth of HCC in the mouse model.

Conclusion: NANO-ASODNs can significantly suppress the growth of HCC in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / genetics
  • Cytokines / therapeutic use*
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Midkine
  • Molecular Sequence Data
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / therapeutic use*
  • Random Allocation
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers, Tumor
  • Cytokines
  • Oligonucleotides, Antisense
  • alpha-Fetoproteins
  • Midkine