Role of the novel HSP90 inhibitor AUY922 in hepatocellular carcinoma: Potential for therapy.
Role of the novel HSP90 inhibitor AUY922 in hepatocellular carcinoma: Potential for therapy.
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DOI：
10.3892/mmr.2015.3725
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发表时间：
2015-08
影响因子：
3.4
通讯作者：
Bao Y
中科院分区：
文献类型：
--
作者：
Cheng W;Ainiwaer A;Xiao L;Cao Q;Wu G;Yang Y;Mao R;Bao Y
本研究的目的是确定参与肿瘤血管生成的热休克蛋白90(HSP90)与肝细胞癌(HCC)的相关性，并评价HSP90抑制剂AUY922在肝细胞癌中的作用。采用免疫组织化学方法检测76例肝细胞癌组织中HSP90的表达和微血管密度(MVD)。免疫印迹法检测HSP90在肝癌组织和不同肝癌细胞系中的表达。研究了AUY922热休克蛋白90抑制剂作用时间和浓度对人肝癌细胞株HepG2的影响。用四甲基偶氮唑盐比色法和Transwell法检测不同浓度AUY922处理后细胞的迁移情况。肝细胞癌组织中HSP90阳性率为88.16%(67/76)，而正常肝组织中HSP90阳性率为16.67%(4/24)。热休克蛋白90在肝细胞癌和正常肝组织中的表达差异有统计学意义(P<；0.001)。HSP90阳性表达的肿瘤微血管密度显著高于HSP90阴性表达的肿瘤(分别为82.8±12.44vs.23.8±8.07；P<；0.001)。热休克蛋白90的表达水平与微血管密度呈正相关(r_S=0.724；P<；0.001)。AUY922以时间和浓度依赖的方式抑制HepG2细胞的增殖，AUY922可明显抑制细胞的迁移。提示HSP90可能参与了人肝细胞癌的血管生成过程，特异性的HSP90抑制剂AUY922在肝癌的治疗中具有一定的治疗作用。因此，HSP90可能是肝癌分子靶向治疗的一个选择性靶点。
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.
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NVP-AUY922：一种小分子 HSP90 抑制剂，在临床前乳腺癌模型中具有有效的抗肿瘤活性。
DOI：
10.1186/bcr1996
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Jensen MR;Schoepfer J;Radimerski T;Massey A;Guy CT;Brueggen J;Quadt C;Buckler A;Cozens R;Drysdale MJ;Garcia-Echeverria C;Chène P
通讯作者：
Chène P
影响因子：
3.8
作者：
Gartner, Elaina M.;Silverman, Paula;Simon, Michael;Flaherty, Lawrence;Abrams, Judith;Ivy, Percy;LoRusso, Patricia M.
通讯作者：
LoRusso, Patricia M.
影响因子：
3
作者：
Eiseman, JL;Lan, J;Egorin, MJ
通讯作者：
Egorin, MJ
DOI：
10.1038/nrc2887
发表时间：
2010-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Trepel J;Mollapour M;Giaccone G;Neckers L
通讯作者：
Neckers L
影响因子：
11.2
作者：
Eccles, Suzanne A.;Massey, Andy;Workman, Paul
通讯作者：
Workman, Paul