Study on in vitro reversing multidrug resistance of human breast cancer cells by buthionine sulfoximine / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the effect of BSO administration on the multidrug resistance (MDR) transformation of human breast cancer cell line in vitro. METHODS: The intracellular GSH content was measured by glutathione reductase recycling assay; the 50% inhibitory concentration (IC50) of ADM was measured by MTT assay, then the multidrug resistance property and multidrug resistance reversal times were determined; the apoptosis rate and cell cycle of MCF-7/ADM cell both before and after BSO administration were measured by flow cytometry. RESULTS: The level of GSH in MCF-7/ADM cells was significantly higher than that in MCF-7 cells; the BSO treatment exerted significant inhibitory effect on the synthesis of GSH in MCF-7/ADM while slight effect on MCF-7 cell; The IC50 of ADM in MCF-7/ADM cells was decreased by BSO of certain doses, the multidrug resistance reversal times by BSO at concentrations of 50, 100, 200, 400, and 800 μmol · L-1 were 1.25, 2.02, 8.42, 12.65, and 9.71 respectively, but BSO had no such effect on MCF-7 cell. The value of apoptosis rate and the cells accumulated in Go/GI phase increased significantly when BSO and ADM were simultaneously used compared with using ADM merely. CONCLUSION: BSO can potentially reverse the MDR of MCF-7/ADM cells by inhibition of GSH synthesis in vitro, and the effect may be achieved by inducing apoptotic cell death. Copyright 2012 by the Chinese Pharmaceutical Association.