Study For Up-regulating Doxorubicin Sensitivity Of MCF-7/ADM Cell Line By Buthionine Sulfoximine

Objective To evaluate the feasibility and study the mechanism of buthionine sulfoximine (BSO) as an effective sensitizer to overcome Doxorubicin (ADM) resistance of human breast cancer cell line MCF-7/ADM.Methods The50%inhibitory concentration (IC50) of ADM was measured by MTT assay following by the determination of the multidrug resistance property and multidrug resistance reversal; The intracellular glutathione (GSH) content was measured by glutathione reductase recycling assay; the enzyme activity of glutathione S-transferase (GST)was measured by GST kit; apoptosis rate of MCF-7/ADM cell was measured by flow cytometry.Result The IC50level of ADM in MCF-7/ADM cells was significantly higher than that in MCF-7cells(1185.5μg/ml vs104.9μg/ml);There was no significant inhibitory effect to MCF-7/ADM with BSO under0.25mg/ml, hence, the experiment concentration of BSO confirmed as0.25mg/ml. The IC50of ADM in MCF-7/ADM was66.5μg/ml and494.5μg/ml with or without BSO, respectively. The multidrug resistance reversal multiple was7.43. The GSH level was decreased in BSO group and increased in ADM group, the combination group was significantly decreased compare with ADM group. The activity of GST was decreased in BSO group. The activity of GST in combination group was decreased within the first24hours and then was increased compared with ADM group. The ratio of apoptosis rate increased significantly in BSO and ADM group compared with ADM group.Conclusion BSO can potentially reverse the ADM resistance of MCF-7/ADM cell line by inhibiting GSH synthesis in vitro, the effect may be achieved by inducing cell apoptosis.