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Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway

PURPOSE: Hepatocellular carcinoma (HCC), has a very high mortality rate and is the most common type of liver cancer. Clotrimazole, a traditional antifungal drug, has garnered considerable attention as a therapeutic strategy for HCC. However, its effects against the migration and invasion of HCC cell...

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Autores principales: Liu, Xudong, Gao, Jie, Sun, Yaohui, Zhang, Feng, Guo, Wenzhi, Zhang, Shuijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976522/
https://www.ncbi.nlm.nih.gov/pubmed/35378926
http://dx.doi.org/10.2147/DDDT.S354205
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author Liu, Xudong
Gao, Jie
Sun, Yaohui
Zhang, Feng
Guo, Wenzhi
Zhang, Shuijun
author_facet Liu, Xudong
Gao, Jie
Sun, Yaohui
Zhang, Feng
Guo, Wenzhi
Zhang, Shuijun
author_sort Liu, Xudong
collection PubMed
description PURPOSE: Hepatocellular carcinoma (HCC), has a very high mortality rate and is the most common type of liver cancer. Clotrimazole, a traditional antifungal drug, has garnered considerable attention as a therapeutic strategy for HCC. However, its effects against the migration and invasion of HCC cells as well as the associated underlying mechanisms remain unclear. Therefore, in this study, we investigated its effects on HCC and attempted to elucidate the underlying molecular mechanisms. METHODS: CCK-8 was used to investigate the inhibitory effect of clotrimazole on the proliferation of different types of HCC cells, and wound healing and transwell assays were performed to investigate its inhibitory effect on the invasion and migration of the HCC cells. Further, western blotting was employed to detect changes in the expression levels of epithelial mesenchymal transition (EMT)-related proteins, extracellular-regulated protein kinases (ERK), p-ERK, p65, and p-p65. We also used ERK activators in combination with clotrimazole to treat the HCC cell lines. RESULTS: Clotrimazole inhibited the invasion and migration of HCC cells, and mechanistically, it exerted these anti-tumor effects via EMT by repressing ERK phosphorylation. CONCLUSION: These findings suggest that clotrimazole inhibits HCC metastasis by repressing EMT in an ERK dephosphorylation-dependent manner.
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spelling pubmed-89765222022-04-03 Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway Liu, Xudong Gao, Jie Sun, Yaohui Zhang, Feng Guo, Wenzhi Zhang, Shuijun Drug Des Devel Ther Original Research PURPOSE: Hepatocellular carcinoma (HCC), has a very high mortality rate and is the most common type of liver cancer. Clotrimazole, a traditional antifungal drug, has garnered considerable attention as a therapeutic strategy for HCC. However, its effects against the migration and invasion of HCC cells as well as the associated underlying mechanisms remain unclear. Therefore, in this study, we investigated its effects on HCC and attempted to elucidate the underlying molecular mechanisms. METHODS: CCK-8 was used to investigate the inhibitory effect of clotrimazole on the proliferation of different types of HCC cells, and wound healing and transwell assays were performed to investigate its inhibitory effect on the invasion and migration of the HCC cells. Further, western blotting was employed to detect changes in the expression levels of epithelial mesenchymal transition (EMT)-related proteins, extracellular-regulated protein kinases (ERK), p-ERK, p65, and p-p65. We also used ERK activators in combination with clotrimazole to treat the HCC cell lines. RESULTS: Clotrimazole inhibited the invasion and migration of HCC cells, and mechanistically, it exerted these anti-tumor effects via EMT by repressing ERK phosphorylation. CONCLUSION: These findings suggest that clotrimazole inhibits HCC metastasis by repressing EMT in an ERK dephosphorylation-dependent manner. Dove 2022-03-29 /pmc/articles/PMC8976522/ /pubmed/35378926 http://dx.doi.org/10.2147/DDDT.S354205 Text en © 2022 Liu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Liu, Xudong
Gao, Jie
Sun, Yaohui
Zhang, Feng
Guo, Wenzhi
Zhang, Shuijun
Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway
title Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway
title_full Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway
title_fullStr Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway
title_full_unstemmed Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway
title_short Clotrimazole Inhibits HCC Migration and Invasion by Modulating the ERK-p65 Signaling Pathway
title_sort clotrimazole inhibits hcc migration and invasion by modulating the erk-p65 signaling pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976522/
https://www.ncbi.nlm.nih.gov/pubmed/35378926
http://dx.doi.org/10.2147/DDDT.S354205
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