Effects Of 17-allylamino-17-demethoxygeldanamycin On The Growth Cycle And Apoptosis Of Bile Duct Cancer Cell Line QBC939

Objective:To study the effects Of heat shock protein 90 (HSP90) inhibitors 17-allylamino-17-demethoxygeldanamycin(17-AAG) induced bile duct cancer cell growth and related mechanisms.Methods:1. MTT assay was used to detect the growth inhibition of QBC939 cells.2. Cell cycle and apoptosis were analyzed by flow cytometry.3. The cell morphology was observed with Wright-Giemsa attaining.4. Alteration of CDK1 and C-e-rbB2 being treated with 17-AAG were measured by immunohistochemistry.Results:1. 17-AAG significantly inhibited growth of QBC939 cells in vitro in a dose-dependent manner with an IC50 value at 1.0umol/l.2. Exposure for 36 hours,17-AAG causes cycle arrested at the G2 phase from 11.90±0.78 percent to 40.33±0.91 percent, with S-phase reduction.3. Exposure for 48 hours,17-AAG(0,0.5,1.0,5.0umol/l) causes cell apoptosis and mainly expressed in early apoptosis, respectively0.43%±0.35%,7.50%±2.59%,19.87%±5.06%,25.30%±2.85%. compared to that in control cells(0umol/l 17- AAG), was reduced significantly.4. The cell morphology was observed by the Wright-Giemsa attaining,and Showed the morphological changes of apoptosis.5. The level of CDK1 and C-e-rbB2 expression in QBC939 cells being treated with 17-AAG, compared to that in control cells, was reduced significantly.Conclusion:17-AAG inhibits Hsp90 chaperone function,and reduces CDK1 and C-erbB2 expression, inhibiting cell proliferation and induceing Cell cycle arrest and apoptosis.