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

INTRODUCTIONKnowledge of stroke symptoms is associated with seeking medical attention early, and knowledge of risk factors is an essential factor in stroke prevention. In this study, we evaluated the level of stroke literacy in Singapore.

MATERIALS AND METHODSA cross-sectional study of Singapore citizens and permanent residents aged 21 years and above was conducted in a public housing estate. Participants were randomly sampled using multi-stage stratified sampling. Assessment of awareness of stroke symptoms and risk factors was performed using open-ended questions. In total, 687 respondents were recruited, with a response rate of 69.7%.

RESULTSOverall, 52.4% of respondents identified the brain as the source of pathology, and 47.6% could cite at least 1 of the 3 FAST symptoms (facial droop, arm weakness and speech difficulty), while 40% could name 2 or more of 7 established risk factors for stroke (high blood pressure, high cholesterol, cigarette smoking, diabetes mellitus, older age, previous heart attacks and stroke). Respondents at higher risk of stroke (older individuals and those with stroke risk factors) did not have greater awareness of stroke symptoms and risk factors. The majority of respondents reported they would seek immediate medical care if they experienced stroke symptoms. Only 59.4% knew the emergency ambulance service telephone number.

CONCLUSIONIn a sample of Singaporean adults residing in a public housing estate, we found evidence of poor stroke literacy, highlighting the need for comprehensive population-based education efforts. There is a role for opportunistic education among those at higher risk of stroke.

Adult ; Aged ; Cross-Sectional Studies ; Female ; Health Literacy ; Humans ; Male ; Middle Aged ; Public Housing ; Risk Factors ; Singapore ; Socioeconomic Factors ; Stroke ; Surveys and Questionnaires ; Young Adult