Role of 17-AAG in inducing apoptosis and cell cycle arrest of HCT-15 cells

AIM: To investigate the effects of 17-AAG on apoptosis and cell cycle of HCT-15 cells and to clarify the related mechanisms. METHODS: MTT method was employed to evaluate the inhibitory effects of 17-AAG with Aifferent time and different doses on the proliferation of HCT-15 cells. The cells were stained with Annexin V-FITC/propidiumiodide and measured by flow cytometry. The expression of STAT3, cyclin D1, Cyt C, caspase 9 and caspase 3 at mRNA and protein levels was determined by RT-PCR and Western blotting. RESULTS: Treatment with 17-AAG at concentration of 1.25~20 mg/L for 24 h and 48 h significantly inhibited the activity of HCT-15 cells at both time-and concentration-dependent manners. Treatment with 17-AAG at concentrations of 0.425, 0.85 and 1.7 mg/L for 48 h significantly induced apoptosis and cell cycle arrest of HCT-15 cells. The exposure of 17-AAG at concentrations of 0.425, 0.85 and 1.7 mg/L for 48 h to the HCT-15 cells significantly down-regulated the expression of STAT3 and cyclin D1 at mRNA and protein levels, but up-regulated Cyt C, caspase 9 and caspase 3 mRNA and protein in a concentration-dependent manner. CONCLUSION: 17-AAG inhibits the cell activity, induces apoptosis and G₁ arrest by down-regulating the expression of cyclin D1, and promoting the mitochondria apoptosis through STAT3 pathway.