Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin resistant human breast cancer cell line.
In malignant cells multidrug resistance (MDR) is frequently associated with the expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts as an ATP-dependent efflux pump causing a decreased intracellular accumulation of structurally unrelated natural anticancer agents such as anthracyclines. Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene product P-gp. In our experiments the revertant activity of medroxyprogesterone acetate (MPA) in comparison to that of the well known revertant agent verapamil (VRP) was investigated. In vitro tests were carried out on a DX-resistant variant (CG5/DX) obtained in our laboratory from the parental CG5 human breast cancer cell line by continuous exposure to the drug. The ability of MPA to modulate intracellular DX accumulation and to reverse MDR was evaluated. MPA appeared more active than VRP in reversing MDR, suggesting a possible role of this synthetic progestin as chemosensitizing agent in the clinical management of anthracycline-resistant breast cancer.
Zibera
C
C
Divisione di Oncologia Medica, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS, Pavia, Italy.
Gibelli
N
N
Maestri
L
L
Della Cuna
G R
GR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D001943:Breast Neoplasms; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D017258:Medroxyprogesterone Acetate; D014700:Verapamil