Zhu Jingjuan, Zhu Yanbiao, Qi Weiwei, Qiu Wensheng
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Department of General Surgery, Beicheng Hospital of Juye County, Heze, Shandong 274900, P.R. China.
Oncol Lett. 2015 Aug;10(2):941-945. doi: 10.3892/ol.2015.3299. Epub 2015 Jun 2.
The aim of the present study was to investigate the effects of the heat shock protein (HSP)90 inhibitor AUY922 on the proliferation and migratory ability of renal cell carcinoma (RCC) cells. The expression of HSP90 was measured using western blotting and quantitative polymerase chain reaction in the ACHN and 786-O cell RCC lines, and also in the immortalized normal human proximal tubule epithelium HK-2 cell line. The effects of the time and concentration of AUY922 administration were investigated in the ACHN and 786-O cells, and the cell proliferation was measured using an MTT assay. A Transwell assay was performed to evaluate the migratory ability of ACHN cells following treatment with AUY922 at concentrations of 10, 50 and 100 nM. Western blot analysis and reverse transcription polymerase chain reaction revealed that HSP90 mRNA and protein were overexpressed in the two RCC cell lines compared with the HK-2 cell line. AUY922 inhibited the proliferation of the ACHN and 786-O cells in a time- and concentration-dependent manner, and the migratory ability of the ACHN cells was markedly suppressed subsequent to treatment with AUY922. The present data suggest that the pathogenesis of human RCC may be mediated by HSP90. It was also indicated that the specific HSP90 inhibitor AUY922 plays a therapeutic role in the treatment of RCC, and therefore, HSP90 may be a selective target for molecular-targeted treatments of RCC.
本研究的目的是探讨热休克蛋白(HSP)90抑制剂AUY922对肾细胞癌(RCC)细胞增殖和迁移能力的影响。采用蛋白质免疫印迹法和定量聚合酶链反应检测ACHN和786 - O肾癌细胞系以及永生化正常人近端肾小管上皮HK - 2细胞系中HSP90的表达。研究了ACHN和786 - O细胞中AUY922给药时间和浓度的影响,并采用MTT法检测细胞增殖。进行Transwell实验以评估用10、50和100 nM浓度的AUY922处理后ACHN细胞的迁移能力。蛋白质免疫印迹分析和逆转录聚合酶链反应显示,与HK - 2细胞系相比,两种肾癌细胞系中HSP90 mRNA和蛋白均过表达。AUY922以时间和浓度依赖性方式抑制ACHN和786 - O细胞的增殖,并且AUY922处理后ACHN细胞的迁移能力明显受到抑制。目前的数据表明,人类肾细胞癌的发病机制可能由HSP90介导。还表明,特异性HSP90抑制剂AUY922在肾细胞癌治疗中发挥治疗作用,因此HSP90可能是肾细胞癌分子靶向治疗的选择性靶点。