Killing effect of 17-allylamino-17-demethoxygeldanamycin on a breast cancer cell line / 医学研究生学报

ABSTRACT

Objective:To study the anti-proliferation effects of a heat shock protein 90(Hsp90) inhibitor,17-allylamino-17-demethoxygeldanamycin(17-AAG),on a human breast cancer cell line,SKBr3,and related mechanism.Methods:MTT assay was used to detect the growth inhibition of SKBr3 cells.Cell cycle and apoptosis were analyzed by flow cytometry.Alteration of human epidermal growth factor receptor 2(HER2) in SKBr3 cells being treated with 17-AAG were measured by immunohistochemistry.Results:17-AAG significantly inhibited growth of SKBr3 cells in vitro in a dose-dependent manner with an IC_(50) value at 3.09 ?g/ml.Under concentrations of 0,0.625,1.250,2.500,5.000 and 10.000(?g/ml,)the percentages of cell apoptosis were(1.03?0.08)%,(3.68?0.67)%,(7.06?1.12)%,(11.23?1.36)%,(20.32?1.98)%,and(31.65?2.96)%;the percentages of cells at G_(0)/G_(l) phase were 58.61%,54.34%,49.55%,43.73%,35.52%,and 27.46%;the percentages of cells at S phase were 29.57%,25.21%,19.65%,22.98%,19.71%,and 15.46%;the percentages of cells at G_(2) /M phase were 11.82%,20.45%,30.18%,33.29%,44.77%,and 57.08%,respectively.The level of HER2 expression in SKBr3 cells being treated with 17-AAG,compared to that in control cells,was reduced significantly.Conclusion:17-AAG can inhibit the growth of human breast cancer cell and enhance its apoptosis.It may be a promising anti-tumor drug.