title: Role of the novel HSP90 inhibitor AUY922 in hepatocellular carcinoma: Potential for therapy.
abstract: The aim of the present study was to determine the correlation between hepatocellular carcinoma (HCC) and heat shock protein 90 (HSP90), involved in tumor angiogenesis, and to evaluate the effect of AUY922, a HSP90 inhibitor, in HCC. The expression of HSP90 and microvessel density (MVD) were measured in tissue samples from 76 patients with HCC by immunohistochemistry. Western blot analysis was performed to detect the expression of HSP90 in the HCC tissues and different HCC cell lines. The effects of time and concentration treatment with the AUY922 HSP90 inhibitor were investigated in HepG2 cells. Cell proliferation was measured using an MTT assay and a Transwell assay was performed to evaluate the migration of the HepG2 cells following treatment with different concentrations of AUY922. Positive staining of HSP90 was observed in 88.16% (67/76) of the HCC tissues, compared with 16.67% (4/24) of the normal tissues. The difference in the expression of HSP90 between the HCC and normal tissues was statistically significant (P<0.001). Tumors exhibiting positive expression of HSP90 had significantly higher MVD compared with the HSP90-negative counterparts (82.8 ± 12.44 vs. 23.8 ± 8.07, respectively; P<0.001). The expression levels of HSP90 were positively correlated with MVD in all the tissue samples (r_s=0.724; P<0.001). AUY922 inhibited the proliferation of the HepG2 cells in a time-and concentration-dependent manner, and the migration of HepG2 cells was distinctly suppressed following treatment with AUY922. These data suggested that the angiogenesis of human HCC may be mediated by HSP90, and that the specific HSP90 inhibitor, AUY922, has a therapeutic role in the treatment of HCC. Therefore, HSP90 may represent a selective target in molecularly targeted treatment of HCC.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Aimudula
authors.initials: A
authors.lastname: Ainiwaer
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Mao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, P.R. China.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012118:Resorcinols / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: C528044:5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; D018841:HSP90 Heat-Shock Proteins; D007555:Isoxazoles; D012118:Resorcinols