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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: Wu, Tiangen, Ke, Yang, Tang, Haoran, Liao, Chen, Li, Jinze, Wang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605295/
https://www.ncbi.nlm.nih.gov/pubmed/34853813
http://dx.doi.org/10.1016/j.omto.2021.06.005
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author Wu, Tiangen
Ke, Yang
Tang, Haoran
Liao, Chen
Li, Jinze
Wang, Lin
author_facet Wu, Tiangen
Ke, Yang
Tang, Haoran
Liao, Chen
Li, Jinze
Wang, Lin
author_sort Wu, Tiangen
collection PubMed
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.
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spelling pubmed-86052952021-11-30 Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma Wu, Tiangen Ke, Yang Tang, Haoran Liao, Chen Li, Jinze Wang, Lin Mol Ther Oncolytics Original Article 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. American Society of Gene & Cell Therapy 2021-06-12 /pmc/articles/PMC8605295/ /pubmed/34853813 http://dx.doi.org/10.1016/j.omto.2021.06.005 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Wu, Tiangen
Ke, Yang
Tang, Haoran
Liao, Chen
Li, Jinze
Wang, Lin
Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma
title 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_short 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605295/
https://www.ncbi.nlm.nih.gov/pubmed/34853813
http://dx.doi.org/10.1016/j.omto.2021.06.005
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