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

The acquisition of multidrug resistance in human ovarian carcinoma A2780 cells was investigated after chronic exposure to free mesochlorin e(6) monoethylenediamine (Mce(6)) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound Mce(6) (P(GG)-Mce(6)). The dose that inhibits growth by 50% (IC50) was determined for free Mce(6) (2.09 +/- 0.32 mu M) and P(GG)-Mce(6) (204.15 +/- 28.97 mu M) 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)-Mce(6) 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. (C) 2000 Elsevier Science Ltd. All rights reserved.