Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

Oncogene. 2004 Jan 29;23(4):945-55. doi: 10.1038/sj.onc.1207237.

Abstract

Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Base Sequence
  • Cell Line, Tumor
  • DNA Primers
  • Flow Cytometry
  • Glypicans
  • Heparan Sulfate Proteoglycans / genetics
  • Heparan Sulfate Proteoglycans / physiology*
  • Humans
  • Mitoxantrone / pharmacology*
  • RNA, Messenger / genetics
  • Stomach Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • DNA Primers
  • Glypicans
  • Heparan Sulfate Proteoglycans
  • RNA, Messenger
  • Mitoxantrone