Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma

The aldose reductase inhibitor Fidarestat has been noted to have efficacy in treating a variety of tumors. To define its role in hepatocellular carcinoma (HCC), we induced a HCC xenograft model in mice, which were treated with different doses of Fidarestat. The amounts of natural killer (NK) cells a...

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Autores principales:	Tiangen Wu, Yang Ke, Haoran Tang, Chen Liao, Jinze Li, Lin Wang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Fidarestat AKR1B10 natural killer cells hepatocellular carcinoma glycolysis tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/eb3feba7ac6042e69abcc61b89e7756f
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spelling	oai:doaj.org-article:eb3feba7ac6042e69abcc61b89e7756f2021-11-18T04:50:27ZFidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma2372-770510.1016/j.omto.2021.06.005https://doaj.org/article/eb3feba7ac6042e69abcc61b89e7756f2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S237277052100084Xhttps://doaj.org/toc/2372-7705The aldose reductase inhibitor Fidarestat has been noted to have efficacy in treating a variety of tumors. To define its role in hepatocellular carcinoma (HCC), we induced a HCC xenograft model in mice, which were treated with different doses of Fidarestat. The amounts of natural killer (NK) cells and related inflammatory factors were detected in the serum of the mice. Fidarestat inhibited HCC tumor growth and lung metastasis in vivo and increased NK cell number as well as levels of NK cell-related inflammatory factors in mouse serum. NK cells were then co-cultured with the HCC cell line in vitro to detect effects on HCC cell progression after Fidarestat administration. The glycolysis activity of the NK cells was evaluated by extracellular acidification rate, while aldo-keto reductase family 1 member B10 (AKR1B10) expression was detected by western blot analysis. Administration of Fidarestat downregulated the expression of AKR1B10 in NK cells and promoted NK cell glycolysis to enhance their killing activity against HCC cells. However, depletion of NK cells or upregulation of AKR1B10 attenuated the anticancer activity of Fidarestat. Taken together, Fidarestat downregulated AKR1B10 expression in NK cells to promote NK cell glycolysis, thereby alleviating HCC progression.Tiangen WuYang KeHaoran TangChen LiaoJinze LiLin WangElsevierarticleFidarestatAKR1B10natural killer cellshepatocellular carcinomaglycolysistumor microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 420-431 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fidarestat AKR1B10 natural killer cells hepatocellular carcinoma glycolysis tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Fidarestat AKR1B10 natural killer cells hepatocellular carcinoma glycolysis tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tiangen Wu Yang Ke Haoran Tang Chen Liao Jinze Li Lin Wang Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
description	The aldose reductase inhibitor Fidarestat has been noted to have efficacy in treating a variety of tumors. To define its role in hepatocellular carcinoma (HCC), we induced a HCC xenograft model in mice, which were treated with different doses of Fidarestat. The amounts of natural killer (NK) cells and related inflammatory factors were detected in the serum of the mice. Fidarestat inhibited HCC tumor growth and lung metastasis in vivo and increased NK cell number as well as levels of NK cell-related inflammatory factors in mouse serum. NK cells were then co-cultured with the HCC cell line in vitro to detect effects on HCC cell progression after Fidarestat administration. The glycolysis activity of the NK cells was evaluated by extracellular acidification rate, while aldo-keto reductase family 1 member B10 (AKR1B10) expression was detected by western blot analysis. Administration of Fidarestat downregulated the expression of AKR1B10 in NK cells and promoted NK cell glycolysis to enhance their killing activity against HCC cells. However, depletion of NK cells or upregulation of AKR1B10 attenuated the anticancer activity of Fidarestat. Taken together, Fidarestat downregulated AKR1B10 expression in NK cells to promote NK cell glycolysis, thereby alleviating HCC progression.
format	article
author	Tiangen Wu Yang Ke Haoran Tang Chen Liao Jinze Li Lin Wang
author_facet	Tiangen Wu Yang Ke Haoran Tang Chen Liao Jinze Li Lin Wang
author_sort	Tiangen Wu
title	Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
title_short	Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
title_full	Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
title_fullStr	Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
title_full_unstemmed	Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
title_sort	fidarestat induces glycolysis of nk cells through decreasing akr1b10 expression to inhibit hepatocellular carcinoma
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/eb3feba7ac6042e69abcc61b89e7756f
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Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma

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