Chronic exposure of human ovarian carcinoma cells to free or HPMA copolymer-bound mesochlorin e6 does not induce P-glycoprotein-mediated multidrug resistance.

Abstract

The acquisition of multidrug resistance in human ovarian carcinoma A2780 cells was investigated after chronic exposure to free mesochlorin e6 monoethylenediamine (Mce6) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound Mce6 (P(GG)-Mce6). The dose that inhibits growth by 50% (IC50) was determined for free Mce6 (2.09 +/- 0.32 microM) and P(GG)-Mce6 (204.15 +/- 28.97 microM) to utilize similar effective doses of drug. A total of 14 drug exposures were performed over a period of 78 days. Cells were characterized by IC50 dose, MDR1 gene expression and anti-human P-glycoprotein (P-gp) antibody binding after each drug exposure. At the conclusion of the experiment, neither the A2780 cells habitually exposed to free Mce6 or P(GG)-Mce6 were significantly different than the control A2780 cells indicating cells did not acquire a MDR phenotype. The doxorubicin (DOX)-resistant A2780/AD cells served as a positive control.

• Authors: M Tijerina, K D Fowers, P Kopecková, J Kopecek
• Journal: Biomaterials (Biomaterials) Vol. 21 Issue 21 Pg. 2203-10 (Nov 2000) ISSN: 0142-9612 [Print] Netherlands
• PMID: 10985494 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antibodies, Monoclonal
• Antineoplastic Agents
• Immunoglobulin G
• Mesoporphyrins
• Methacrylates
• N-(2-hydroxypropyl)methacrylamide copolymer-bound Mce(6)
• Neoplasm Proteins
• Pharmaceutical Vehicles
• Porphyrins
• meso-chlorin e(6) monoethylene diamine
• Doxorubicin
• hydroxypropyl methacrylate

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, immunology, metabolism)
• Animals
• Antibodies, Monoclonal (immunology)
• Antineoplastic Agents (administration & dosage, pharmacology)
• Carcinoma (pathology)
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (drug effects)
• Genes, MDR
• Humans
• Immunoglobulin G (immunology)
• Mesoporphyrins
• Methacrylates (administration & dosage, pharmacology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Proteins (genetics, immunology, metabolism)
• Ovarian Neoplasms (pathology)
• Pharmaceutical Vehicles
• Phenotype
• Porphyrins (administration & dosage, pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured (drug effects)