Potent antitumor activity of HSP90 inhibitor AUY922 in adrenocortical carcinoma.
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.
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.
Junchao
J
Huang
Chengchao
C
Sun
Ting
T
Zhang
Lei
L
Pan
Suqing
S
Wang
Qiqiang
Q
He
Dejia
D
Li
D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000037:antagonists & inhibitors*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012118:Resorcinols / Q000494:pharmacology*
C528044:5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D007555:Isoxazoles; D012118:Resorcinols