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新型热休克蛋白90（HSP90）抑制剂NVP - AUY922在体外和体内均能抑制恶性嗜铬细胞瘤的进展。

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo.

作者信息

Lian Jianpo, Lin Dengqiang, Xie Xing, Xu Yunze, Xu Lieyu, Meng Li, Zhu Yu

机构信息

Department of Urology, Ruijin Hospital.

Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

出版信息

Onco Targets Ther. 2017 Apr 19;10:2219-2226. doi: 10.2147/OTT.S130236. eCollection 2017.

DOI:10.2147/OTT.S130236
PMID:28458565
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5403128/
Abstract

PURPOSE

Malignant pheochromocytoma (PCC) is a rare tumor with a very poor prognosis and no effective treatments. The aim of this study was to assess the efficacy of a novel second-generation synthetic heat-shock protein 90 (HSP90) inhibitor, NVP-AUY922, to treat malignant PCC in vitro and in vivo.

MATERIALS AND METHODS

Cell Counting Kit-8 (CCK-8) and Transwell assays were used to assess the effects of NVP-AUY922 on the proliferation and migration of the PCC cell line PC12. Flow cytometry was used to determine the effects of NVP-AUY922 on apoptosis and cell-cycle progression. Activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB/AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling was measured using a Western blot analysis. In vivo, a mouse xenograft model was used to test the effects of intraperitoneal injection of NVP-AUY922 on tumor growth.

RESULTS

NVP-AUY922 was found to be cytotoxic in PC12 cells at lower concentrations compared with 17-allylamino-17-demethoxygeldanamcyin (17-AAG). NVP-AUY922 inhibited the proliferation of PC12 cells in a time- and concentration-dependent manner and decreased the rate of migration of PC12 cells. Furthermore, we found that HSP90 inhibition induced cell-cycle arrest and apoptosis. In vivo, administration of NVP-AUY922 reduced PCC tumor growth without significant weight loss. Finally, we observed the modulation of MEK/ERK and PI3K/AKT signaling in response to NVP-AUY922 exposure.

CONCLUSION

NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC.

摘要

目的

恶性嗜铬细胞瘤（PCC）是一种罕见肿瘤，预后极差且无有效治疗方法。本研究旨在评估新型第二代合成热休克蛋白90（HSP90）抑制剂NVP - AUY922在体外和体内治疗恶性PCC的疗效。

材料与方法

使用细胞计数试剂盒 - 8（CCK - 8）和Transwell实验评估NVP - AUY922对PCC细胞系PC12增殖和迁移的影响。采用流式细胞术测定NVP - AUY922对细胞凋亡和细胞周期进程的影响。使用蛋白质免疫印迹分析检测磷脂酰肌醇 - 3激酶（PI3K）/蛋白激酶B（PKB/AKT）和丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）信号通路的激活情况。在体内，使用小鼠异种移植模型测试腹腔注射NVP - AUY922对肿瘤生长的影响。

结果

与17 - 烯丙胺基 - 17 - 去甲氧基格尔德霉素（17 - AAG）相比，发现NVP - AUY922在较低浓度下对PC12细胞具有细胞毒性。NVP - AUY922以时间和浓度依赖性方式抑制PC12细胞的增殖，并降低PC12细胞的迁移率。此外，我们发现抑制HSP90可诱导细胞周期停滞和凋亡。在体内，给予NVP - AUY922可减少PCC肿瘤生长，且无明显体重减轻。最后，我们观察到NVP - AUY922暴露后MEK/ERK和PI3K/AKT信号通路的调节。

结论

NVP - AUY922在体外和体内均表现出强大的抗PCC活性，是一种有前景的治疗恶性PCC的小分子药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/7e4ea3ebea0c/ott-10-2219Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/9e5c0634599c/ott-10-2219Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/cd20845bfc75/ott-10-2219Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/043a145c81a9/ott-10-2219Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/06ea9566ea8c/ott-10-2219Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/0270d97abf08/ott-10-2219Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/7e4ea3ebea0c/ott-10-2219Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/9e5c0634599c/ott-10-2219Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/cd20845bfc75/ott-10-2219Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/043a145c81a9/ott-10-2219Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/06ea9566ea8c/ott-10-2219Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/0270d97abf08/ott-10-2219Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cee0/5403128/7e4ea3ebea0c/ott-10-2219Fig6.jpg

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本文引用的文献

1
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Pharmaceuticals (Basel). 2011 Oct 25;4(11):1400-1422. doi: 10.3390/ph4111400.
2
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Semin Nucl Med. 2016 May;46(3):203-14. doi: 10.1053/j.semnuclmed.2016.01.011.
3
Hsp90: A Global Regulator of the Genotype-to-Phenotype Map in Cancers.热休克蛋白90：癌症中基因型到表型图谱的全局调节因子。
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Cell Stress Chaperones. 2021 May;26(3):495-504. doi: 10.1007/s12192-021-01193-6. Epub 2021 Feb 24.
4
Advances in adrenal tumors 2018.2018 年肾上腺肿瘤的研究进展。
Endocr Relat Cancer. 2018 Jul;25(7):R405-R420. doi: 10.1530/ERC-18-0138.
5
Sensitization of multidrug-resistant cancer cells to Hsp90 inhibitors by NSAIDs-induced apoptotic and autophagic cell death.非甾体抗炎药诱导的凋亡和自噬性细胞死亡使多药耐药癌细胞对热休克蛋白90抑制剂敏感。
Oncotarget. 2018 Jan 10;9(13):11303-11321. doi: 10.18632/oncotarget.24130. eCollection 2018 Feb 16.
Adv Cancer Res. 2016;129:225-47. doi: 10.1016/bs.acr.2015.11.001. Epub 2015 Nov 29.
4
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Hematol Oncol Clin North Am. 2016 Feb;30(1):135-50. doi: 10.1016/j.hoc.2015.09.006. Epub 2015 Oct 23.
5
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6
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7
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J Mol Endocrinol. 2012 Jul 25;49(2):79-96. doi: 10.1530/JME-12-0028. Print 2012 Oct.
9
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Curr Opin Oncol. 2011 Jul;23(4):367-72. doi: 10.1097/CCO.0b013e3283477ac2.
10
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Cancer Sci. 2011 Jul;102(7):1388-95. doi: 10.1111/j.1349-7006.2011.01944.x. Epub 2011 May 3.