OBJECTIVE Geldanamycin,a natural product of Streptomyces geldanus,binds the heat shock protein 90(Hsp90),a cell chaperone protein that interacts with Bcl-2.In this study,we investigated whether geldanamycin(GA)inhibits proliferation of HeLa cells through induction of apoptosis by decreasing the level of Bcl-2 expression. METHODS HeLa cells,a human cervical cell line,were cultured in vitro and treated with different concentrations of GA(0,0.02,0.2, 2,10μmol/L)for 24 h.or were treated for different lengths of time at a GA concentration of 10μmol/L.Proliferation of the cells was analyzed by an MTT assay,and cell apoptosis was determined by staining the cells with annexin V.In addition,cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semiquantitative polymerase chain reaction(PCR),and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots. RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time-dependent manner.The inhibition was a result of increased cellular apoptotic levels.Further analyses showed that while the mRNA and protein expression levels of Hsp90 were not affected,GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation. CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2,probably through interaction and functional inhibition of Hsp90. OBJECTIVE Geldanamycin, a natural product of Streptomyces geldanus, binds the heat shock protein 90 (Hsp90), a cell chaperone protein that interacts with Bcl-2. In this study, we investigated whether geldanamycin (GA) inhibits proliferation of HeLa cells through induction of METHODS by HeLa cells, a human cervical cell line, were cultured in vitro and treated with different concentrations of GA (0,0.02,0.2, 2,10 μmol / L) for 24 h.or were treated for different lengths of time at a GA concentration of 10 μmol / L. Proliferation of the cells was analyzed by an MTT assay, and cell apoptosis was determined by staining the cells with annexin V. In addition, the cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semiquantitative polymerase chain reaction (PCR), and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots. RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time- dependent manner. inhibition of a result of increased cellular apoptotic levels. Further analyzes showed that while the mRNA and protein expression levels of Hsp90 were not affected, GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation. CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2, probably through interaction and functional inhibition of Hsp90.