ABSTRACT
Objective:To investigate the reversing effect of phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002(LY) and wortmannin (Wort), on the drug resistance of mitoxantrone (MIT)-resistant human breast cancer MCF-7/MIT cells. Methods:Drug-resistant MCF-7/MIT cells were treated with LY or Wort combined with MIT. Cell viability and proliferation were measured using the MTT assay and morphological changes were recorded by microscopy. Intracellular accumulation of MIT in MCF-7/MIT cells was detected by flow cytometry. Mitochondrial membrane potential was determined by rhodamine 123 staining. Cell cycle was examined by propidium iodide staining. Results:LY significantly enhanced the cytotoxicity of MIT to MCF-7/MIT cells. In LY and MIT cotreated cells, the percentage of cells arrested at S and G2/M phases and the mitochondrial membrane potential decreased significantly compared with single LY- or MIT-treated cells. The mechanism was related with increased accumulation of MIT in MCF-7/MIT cells induced by LY. While Wort, another PI3K inhibitor, did not significantly enhance the cytotoxic effects of MIT.Conclusion: The PI3K inhibitor significantly enhances the sensitivity of MCF-7/MIT cells to MIT.