Reversal effects of mifepristone on multidrug resistance(MDR) in drug-resistant breast cancer cell line MCF7/ADR in vitro and in vivo
| العنوان: | Reversal effects of mifepristone on multidrug resistance(MDR) in drug-resistant breast cancer cell line MCF7/ADR in vitro and in vivo |
|---|---|
| المؤلفون: | Li Hua Pan, Da Qiang Li, Zhi Min Shao |
| المصدر: | Chinese Journal of Cancer Research. 16:93-98 |
| بيانات النشر: | Chinese Journal of Cancer Research, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Cancer Research, medicine.diagnostic_test, business.industry, Cell, Mifepristone, Pharmacology, Rhodamine 123, In vitro, Flow cytometry, Multiple drug resistance, chemistry.chemical_compound, medicine.anatomical_structure, Oncology, chemistry, In vivo, medicine, business, Intracellular, medicine.drug |
| الوصف: | Objective: To explore the reversal effect of mifepristone on multidrug resistance (MDR) in drug-resistant human breast cancer cell line MCF7/ADR and its mechanisms. Methods: Expression of MDR1 and MDR-associated protein(MRP) mRNA in MCF7/ADR cells was detected using reverse transcription- polymerase chain reaction(RT-PCR). Western blotting was used to assay the protein levels of P-glycoprotein (P-gp) and MRP. Intracellular rhodamine 123 retention and [3H]vincristine (VCR) accumulation were measured by flow cytometry and liquid scintillation counter, respectively. MTT reduction assay was used to determine the sensitivity of cells to the anticancer agent, adriamycin (ADR). Additionally, a MCF7/ADR cell xenograft model was established to assess the reversal effect of mifeprisone on MDR in MCF7/ADR cells in vivo. Results: Miferpristone dose-dependently down- regulated the expression of MDR1 and MRP mRNA in MCF7/ADR cells, accompanied by a significant decrease in the protein levels of P-gp and MRP. After exposure to 5, 10, and 20 µmol/L mifepristone, MCF7/ADR cells showed a 3.87-, 5.81-, and 7.40-fold increase in the accumulation of intracellular VCR(a known substrate of MRP), and a 2.14—, 4.39—, and 5.53—fold increase in the retention of intracellular rhodamine 123(an indicator of P-gp function), respectively. MTT analysis showed that the sensitivity of MCF7/ADR cells to ADR was enhanced by 7.23—, 13.62—, and 20.96—fold after incubation with mifepristone as above-mentioned doses for 96 h. In vivo, mifepristone effectively restored the chemosensitivity of MCF7/ADR cells to ADR. After 8 weeks of administration with ADR(2 mg·kg−1·d−1) alone or in combination with mifepristone(50 mg·kg−1·d−1), the growth inhibitory rate of xenografted tumors in nude mice was 8.08% and 37.25%, respectively. Conclusion: Mifepristone exerts potent reversal effects on MDR in MCF7/ADR cells in vitro and in vivo through down- regulation of MDR1/P-gp and MRP expression and inhibition of P-gp- and MRP-dependent drug efflux, thus increasing the sensitivity to anticancer drug. |
| تدمد: | 1993-0631 1000-9604 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::25f91237c85b2b3896d4051463b280b0Test https://doi.org/10.1007/s11670-004-0004-zTest |
| رقم الانضمام: | edsair.doi...........25f91237c85b2b3896d4051463b280b0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19930631 10009604 |
|---|