Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

Rui Yang,1,* Qiusha Tang,1,* Fengqin Miao,1 Yanli An,2 Mengfei Li,1 Yong Han,1 Xihui Wang,1 Juan Wang,3 Peidang Liu,1 Rong Chen41School of Medicine, Southeast University, 2Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing, 3Department of I...

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Autores principales:	Yang R, Tang QS, Miao FQ, An YL, Li MF, Han Y, Wang XH, Wang J, Liu PD, Chen R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	thermoresistance CD90+ LCSCs magnetic hyperthermia 17-AAG Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d2de6dff268b47c2b289ea4acdbdd909
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spelling	oai:doaj.org-article:d2de6dff268b47c2b289ea4acdbdd9092021-12-02T07:13:44ZInhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice1178-2013https://doaj.org/article/d2de6dff268b47c2b289ea4acdbdd9092015-12-01T00:00:00Zhttps://www.dovepress.com/inhibition-of-heat-shock-protein-90-sensitizes-liver-cancer-stem-like--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Rui Yang,1,* Qiusha Tang,1,* Fengqin Miao,1 Yanli An,2 Mengfei Li,1 Yong Han,1 Xihui Wang,1 Juan Wang,3 Peidang Liu,1 Rong Chen41School of Medicine, Southeast University, 2Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing, 3Department of Infectious Disease, The Third People’s Hospital of Nantong, Nangtong; 4Department of Oncology, Zhongda Hospital, Nangjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workPurpose: To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice.Methods: CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo.Results: CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia.Conclusion: The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo.Keywords: thermoresistance, CD90+ LCSCs, magnetic hyperthermia, 17-AAGYang RTang QSMiao FQAn YLLi MFHan YWang XHWang JLiu PDChen RDove Medical PressarticlethermoresistanceCD90+ LCSCsmagnetic hyperthermia17-AAGMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 7345-7358 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	thermoresistance CD90+ LCSCs magnetic hyperthermia 17-AAG Medicine (General) R5-920
spellingShingle	thermoresistance CD90+ LCSCs magnetic hyperthermia 17-AAG Medicine (General) R5-920 Yang R Tang QS Miao FQ An YL Li MF Han Y Wang XH Wang J Liu PD Chen R Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
description	Rui Yang,1,* Qiusha Tang,1,* Fengqin Miao,1 Yanli An,2 Mengfei Li,1 Yong Han,1 Xihui Wang,1 Juan Wang,3 Peidang Liu,1 Rong Chen41School of Medicine, Southeast University, 2Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing, 3Department of Infectious Disease, The Third People’s Hospital of Nantong, Nangtong; 4Department of Oncology, Zhongda Hospital, Nangjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workPurpose: To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice.Methods: CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo.Results: CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia.Conclusion: The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo.Keywords: thermoresistance, CD90+ LCSCs, magnetic hyperthermia, 17-AAG
format	article
author	Yang R Tang QS Miao FQ An YL Li MF Han Y Wang XH Wang J Liu PD Chen R
author_facet	Yang R Tang QS Miao FQ An YL Li MF Han Y Wang XH Wang J Liu PD Chen R
author_sort	Yang R
title	Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
title_short	Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
title_full	Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
title_fullStr	Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
title_full_unstemmed	Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
title_sort	inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/d2de6dff268b47c2b289ea4acdbdd909
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Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

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