Huang Junchao, Sun Chengchao, Zhang Ting, Pan Lei, Wang Suqing, He Qiqiang, Li Dejia
Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning, 437100, China.
Tumour Biol. 2014 Aug;35(8):8193-9. doi: 10.1007/s13277-014-2063-1. Epub 2014 May 22.
The objective of this study is to investigate the expression of HSP90 and the effect of HSP90 inhibitor AUY922 in ACC. The expression of HSP90 was measured in tissue samples from 36 human sporadic adrenocortical tumors by immunohistochemistry, Western blotting, and real-time PCR. The effect of AUY922 was tested on SW13 and H295R cells by evaluating cell viability and apoptosis in vitro. Transwell assay was performed to evaluate the migration of SW13 cells after different concentrations of AUY922. Western blot, real-time PCR, and immunohistochemistry revealed that both HSP90 mRNA and protein were obviously expressed in a higher degree in ACC tissues than ACA tissues and normal adrenal tissues (P < 0.01). Positive staining for HSP90 was found in 15 of 20 ACCs (75.00 %) and in 3 of 16 (18.75 %) ACAs. There existed the significant statistical difference (P < 0.001). AUY922 inhibited the proliferation of ACC cells in a time- and concentration-dependent manner, and increasing apoptosis was observed in tumor cells treated with the HSP90 inhibitor. Finally, migration of SW13 cells was distinctly suppressed after undergoing treatment with AUY922. Our data suggest that the specific HSP90 inhibitor AUY922 can play a therapeutic role in treatment of ACC and, thus, HSP90 could qualify as a promising new target in ACC.
本研究的目的是调查热休克蛋白90（HSP90）的表达情况以及HSP90抑制剂AUY922在肾上腺皮质癌（ACC）中的作用。通过免疫组织化学、蛋白质印迹法和实时荧光定量PCR检测了36例人类散发性肾上腺皮质肿瘤组织样本中HSP90的表达。通过评估体外细胞活力和凋亡情况，检测了AUY922对SW13和H295R细胞的作用。进行Transwell实验以评估不同浓度AUY922作用后SW13细胞的迁移情况。蛋白质印迹法、实时荧光定量PCR和免疫组织化学结果显示，与肾上腺皮质腺瘤（ACA）组织和正常肾上腺组织相比，HSP90 mRNA和蛋白在ACC组织中的表达明显更高（P < 0.01）。20例ACC中有15例（75.00%）HSP90呈阳性染色，16例ACA中有3例（18.75%）呈阳性染色。存在显著统计学差异（P < 0.001）。AUY922以时间和浓度依赖性方式抑制ACC细胞的增殖，在用HSP90抑制剂处理后的肿瘤细胞中观察到凋亡增加。最后，用AUY922处理后，SW13细胞的迁移明显受到抑制。我们的数据表明，特异性HSP90抑制剂AUY922在ACC治疗中可发挥治疗作用，因此，HSP90有望成为ACC的一个新的有前景的治疗靶点。
