Chronic exposure of human ovarian carcinoma cells to free or HPMA copolymer-bound mesochlorin e6 does not induce P-glycoprotein-mediated multidrug resistance.
basic_science · Level V
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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.
Medical subject headings
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antineoplastic Agents
- Carcinoma
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Gene Expression Regulation, Neoplastic
- Genes, MDR
- Methacrylates
- Neoplasm Proteins
- Ovarian Neoplasms
- Porphyrins