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• W2155231671 abstract "Background: Methylnaltrexone, a novel peripherally acting opioid receptor antagonist, is used to treat opiate-induced constipation in cancer patients. Its effects on the activities of chemotherapeutic agents, however, have not been evaluated. In this study, the effect of methylnaltrexone on the action of 5-fluorouracil (5-FU) was tested in three human cancer cell lines. Materials and Methods: Treatment was for 72 h and the effects on cell proliferation were measured in human SW-480 colorectal cancer cells, MCF-7 breast cancer cells and non-small cell lung cancer cells in vitro. The apoptotic effect was analyzed by using flow cytometry. The cell cycle and expression of cyclin A were assayed after staining with propidium iodide and cyclin A-fluorescein isothiocyanate. Results: 5-FU decreased the cancer cell growth significantly in all three cancer cell lines in a concentration-dependent manner and methylnaltrexone enhanced the actions of 5-FU. Compared to 5-FU 10 μM alone on SW-480 cells (63.5±1.1% ), on MCF-7 cells (58.3±3.1% ), or on non-small cell lung cancer cells (81.3±1.6% ), 5-FU 10 μM plus methylnaltrexone 1.0 μM reduced cancer cell growth in all three cell lines to 50.2±2.9% for SW-480 cells (p<0.05), 50.0±1.7% for MCF- 7 cells (p<0.05) and 68.7±2.2% for lung cancer cells (p<0.01). Methylnaltrexone alone also showed anti- proliferative activity in the three cell lines. Methylnaltrexone at 1.0 μM, reduced SW-480 cell growth to 81.9±3.7% (p<0.01), MCF-7 cell growth to 85.9±2.4% (p<0.01) and lung cancer cell growth to 85.5±2.2% (p<0.01). Apoptosis was not induced by treatment of SW-480 cells with 1.0 or 10 μM methylnaltrexone for 48 h. However, methylnaltrexone increased the number of cells in the G 1 -phase and decreased the expression of cyclin A. Conclusion: At its therapeutic concentrations for opioid-induced constipation, methyl- naltrexone does not attenuate and in fact may enhance the tumoricidal activity of 5-FU. Enhanced 5-FU activity may be attributed to the distinct pathways of 5-FU and methylnaltrexone, an effect that could give methylnaltrexone a complementary role in the treatment of cancer with chemotherapeutic agents." @default.
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• W2155231671 date "2009-08-01" @default.
• W2155231671 modified "2023-09-24" @default.
• W2155231671 title "Methylnaltrexone, a Peripherally Acting Opioid Receptor Antagonist, Enhances Tumoricidal Effects of 5-FU on Human Carcinoma Cells" @default.
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