肿瘤预防与治疗2019，Vol.32Issue(12)：1081-1087,7.DOI:10. 3969／j. issn. 1674-0904. 2019. 12. 004
HSP90 抑制剂 17-AAG 经下调 HIF-1 α抑制甲状腺未分化癌侵袭*
HSP90 Inhibitor, 17-AAG, Inhibits Invasion of ATC by Down-Regulating HIF-1α
摘要
Abstract
Objective: To probe into the effects of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a potent heat shock protein 90 (HSP90) inhibitor, on invasion of anaplastic thyroid carcinoma ( ATC ), and investigate how HSP90, hypoxia inducible factor-1α ( HIF-1α) and their downstream targets affect ATC cells. Methods: The half maximal inhibito-ry concentration of 17-AAG on 8505c, a ATC cell line, was determined by cell counting kit 8 (CCK8) assay for use in further experiments. How 17-AAG inhibit the invasion ability of ATC cells was tested by transwell cell invasion chamber experiments, and its mechanisms were assessed by western blot and co-immunoprecipitation (CO-IP). Results: In CCK8 assay, 17-AAG in different concentrations inhibited the growth of ATC cells, the effects were said to be dose-dependent. Based on these results, 17-AAG in 0. 5μM and 1μM for 24h were chosen for subsequent assay. The transwell test showed that 17-AAG inhibited the invasion of 8505c in a dose-dependent manner. Western blot results indicated that 17-AAG also decreased HIF-1α expression and expression of matrix metalloproteinase-2 (MMP2) and vascular endothelial growth factor (VEGF) which are invasion-related proteins. CO-IP analysis suggested that HIF-1α and HSP90 formed protein complexes in ATC cells. Rescue experiment further proved that MMP2 and VEGF expres-sion increased after HIF-1α overexpression, which weakened the inhibition of 17-AAG on the invasion ability of ATC cells. Conclusion: 17-AAG may downregulate HIF-1α by regulating the complex formed by HSP90 and HIF-1, resulting in lower expression of MMP2 and VEGF to inhibit the invasion ability of ATC cells.关键词
甲状腺未分化癌/热休克蛋白90/17-丙烯氨基-去甲氧基-格尔德霉素/低氧诱导因子-1α/侵袭Key words
Anaplastic thyroid carcinoma/Heat shock protein 90/Tanespimycin/Hypoxia-inducible factor 1-alpha/In-vasion分类
医药卫生引用本文复制引用
吴昌昊,孙威,秦元,董文武,张文谦,邵亮,张浩..HSP90 抑制剂 17-AAG 经下调 HIF-1 α抑制甲状腺未分化癌侵袭*[J].肿瘤预防与治疗,2019,32(12):1081-1087,7.基金项目
辽宁省"百千万人才工程" (编号:2014921 033) （编号:2014921 033）
沈阳市科学技术计划项目(编号:F16-205-1-41) This study was supported by grants from Liaoning Provincial Department of Human Resources and Social Security ( NO. 2014921033) and Shenyang Bureau Science and Technology (NO. F16-205-1-41). （编号:F16-205-1-41）
