Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) indicated for the medical treatment of myoma. Several theoretical mechanisms help explain how it induces apoptosis and cystic degeneration of a submucous myoma, leading to its expulsion. This paper presents the case of a young nulligravid diagnosed with heavy menstrual bleeding secondary to submucous myoma, who was started on UPA treatment but with very poor compliance. Despite the very short and incomplete course of treatment, degenerative changes still took effect, which led to the expulsion or prolapse of the pedunculated submucous myoma.
ulipristal acetate ; Norpregnadienes ; Leiomyoma ; Apoptosis ; Uterus

OBJECTIVETo study the reversal effect of nomegestrol acetate (NOM) on mutidrug resistance (MDR) in MCF7/ADR and its mechanism.

METHODSUsing tetrazolium dye assay, effects of various concentrations of NOM on sensitivity to ADR in MCF7/ADR was studied. Expression of MDR related genes MDR1, glutathoine S-transferase Pi (GSTpi), Topoisomerase II alpha (Topo II alpha) and MDR related protein (MRP) were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry assay. Using flow cytometry (FCM), intracellular ADR concentration effects on cell cycle were observed.

RESULTSNOM significantly reversed MDR in MCF7/ADR. After NOM 20, 10 and 5 micromol/L treatment, the chemosensitivity to ADR increased to 21, 12 and 8 times. The reversal activity of NOM was stronger than that of the precursor compound megestrol acetate, and was comparable to that of verapamail. After treatment with NOM 5 micromol/L both MDR1 and GSTpi mRNA genes expression began to decline on D2 (P < 0.05, & P < 0.01) and reached the lowest level on D3 (both P < 0.01), but the expression levels began to rise on D6 again (both P < 0.05). The expression of MRP and Topo II alpha gave no significant change. Changes of P-gp and GSTpi protein expressions were similar to those of their mRNA expressions, showing early decline and late rise. Two hours after NOM 20, 10, and 5 micromol/L treatment, intracellular ADR concentration increased 2.7, 2.3 and 1.5 times, respectively. FCM data showed that after forty-eight hours, combined administration of NOM (20 micromol/L) and ADR (from low concentration to high concentration), MCF7/ADR cells showed gradual arrest in the G(2)M phase with the increase of ADR dose.

CONCLUSIONNOM has strong reversal effects on MDR in MCF7/ADR. The reversal takes place via different routes, i.e. down regulating mRNA and protein expression levels of MDR1 and GSTpi, increasing intracellular drug concentration, and enhancing the arrest of ADR in cells at G(2)M phase.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antigens, Neoplasm ; Breast Neoplasms ; genetics ; pathology ; Cell Survival ; drug effects ; DNA Topoisomerases, Type II ; genetics ; metabolism ; DNA-Binding Proteins ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Glutathione S-Transferase pi ; Glutathione Transferase ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Inhibitory Concentration 50 ; Isoenzymes ; genetics ; metabolism ; Megestrol ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Norpregnadienes ; pharmacology ; Progesterone Congeners ; pharmacology ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured ; Verapamil ; pharmacology