title: The heat shock protein 90 inhibitor 17-AAG suppresses growth and induces apoptosis in human cholangiocarcinoma cells.
abstract: The aim of this study was to investigate the effects of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, on the proliferation, cell cycle, and apoptosis of human cholangiocarcinoma (CCA) cells. Cell proliferation and cell cycle distribution were measured by the MTT assay and flow cytometry analysis, respectively. Induction of apoptosis was determined by flow cytometry and Hoechst staining. The expressions of cleaved poly ADP-ribose polymerase (PARP), Bcl-2, Survivin, and Cyclin B1 were detected by Western blot analysis. The activity of caspase-3 was also examined. We found that 17-AAG inhibited cell growth and induced G2/M cell cycle arrest and apoptosis in CCA cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleaved PARP. Moreover, increased caspase-3 activity was also observed in CCA cells treated with 17-AAG. In conclusion, our data suggest that the inhibition of HSP90 function by 17-AAG may provide a promising therapeutic strategy for the treatment of human CCA.
authors.affiliation: The Third Department of Surgery, Liaoning Cancer Hospital and Institute, 44 Xiaoheyan Road, Shenyang, 110042, Liaoning, People's Republic of China, lnszl_zjj@163.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy; D005434:Flow Cytometry; D005562:Formazans / Q000032:analysis; D020869:Gene Expression Profiling; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D013194:Staining and Labeling; D013778:Tetrazolium Salts / Q000032:analysis / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D005562:Formazans; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D013778:Tetrazolium Salts; D013844:Thiazoles; C079782:MTT formazan; C112765:tanespimycin; C022616:thiazolyl blue