Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells.
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.
Wichert
Anke
A
Institute of Pathology, Charité, Campus Mitte, Humboldt University Berlin, Schumannstr 20/21, Berlin D-10117, Germany.
Stege
Alexandra
A
Midorikawa
Yutaka
Y
Holm
Per Sonne
PS
Lage
Hermann
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D005434:Flow Cytometry; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D017931:DNA Primers; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; D008942:Mitoxantrone