Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784602147903504384 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8605295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wutiangen fidarestatinducesglycolysisofnkcellsthroughdecreasingakr1b10expressiontoinhibithepatocellularcarcinoma AT keyang fidarestatinducesglycolysisofnkcellsthroughdecreasingakr1b10expressiontoinhibithepatocellularcarcinoma AT tanghaoran fidarestatinducesglycolysisofnkcellsthroughdecreasingakr1b10expressiontoinhibithepatocellularcarcinoma AT liaochen fidarestatinducesglycolysisofnkcellsthroughdecreasingakr1b10expressiontoinhibithepatocellularcarcinoma AT lijinze fidarestatinducesglycolysisofnkcellsthroughdecreasingakr1b10expressiontoinhibithepatocellularcarcinoma AT wanglin fidarestatinducesglycolysisofnkcellsthroughdecreasingakr1b10expressiontoinhibithepatocellularcarcinoma |