HPMA copolymer-anticancer drug-OV-TL16 antibody conjugates. 3. The effect of free and polymer-bound Adriamycin on the expression of some genes in the OVCAR-3 human ovarian carcinoma cell line

Klaus Kunath, Pavla Kopečková, Tamara Minko, Jindřich Kopeček

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The effect of an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer- Adriamycin-OV-TL16 antibody conjugate [P(GFLG)-ADR-Ab] on OVCAR-3 human ovarian carcinoma cells was studied. A nontargeted HPMA copolymer-ADR conjugate (P(GFLG)-ADR) and free ADR were the controls. The IC50 doses were 0.65, 3.0, and 65 μM for free ADR, targeted P(GFLG)-ADR-Ab conjugate, and nontargeted P(GFLG)-ADR conjugate, respectively. These differences reflect the different mechanisms of cell entry of the compounds evaluated. Free ADR and HPMA copolymer-ADR conjugates had different impacts on the expression of MDR1, MRP, c-fos, c-jun, and bcl-2 genes which encode the P-glycoprotein (MDR1) and the multidrug resistance-associated protein (MRP) efflux pumps, and play an important role in cell death signaling pathways (c-fos, c-jun, and bcl-2). Whereas high doses of free ADR induced MDR1 gene expression, HPMA copolymer-bound ADR appeared to be without effect. On the contrary, expression of the MRP gene was not influenced by free ADR, whereas HPMA copolymer-ADR conjugates seemed to suppress the gene expression in a concentration-dependent manner. There were differences in the expression of c-fos, c-jun, and bcl-2 genes after the incubation of OVCAR-3 cells with free and HPMA copolymer-bound ADR indicating differences in activation of cell death signaling pathways.

Original languageEnglish (US)
Pages (from-to)11-15
Number of pages5
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume49
Issue number1
DOIs
StatePublished - Jan 3 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Keywords

  • Adriamycin
  • Antibody targeting
  • Cytotoxicity
  • Doxorubicin
  • Gene expression
  • HPMA copolymer-drug conjugates
  • Multidrug resistance
  • OV-TL16 antibody
  • Ovarian carcinoma

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