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Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is recognized as the fifth most common cancer and the third most common cause of death in Asian population. Studies reported that HCC is relatively insensitive to radiotherapy (RT); thus, considering how to sensitize HCC to RT is worth to be elucidated. Epidermal growt...

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Autores principales: Liu, Yu‐Chang, Lin, Cheng Hsun, Chen, Kuan‐Tin, Lai, De‐Wei, Hsu, Fei‐Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243161/
https://www.ncbi.nlm.nih.gov/pubmed/37177859
http://dx.doi.org/10.1111/jcmm.17760
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author Liu, Yu‐Chang
Lin, Cheng Hsun
Chen, Kuan‐Tin
Lai, De‐Wei
Hsu, Fei‐Ting
author_facet Liu, Yu‐Chang
Lin, Cheng Hsun
Chen, Kuan‐Tin
Lai, De‐Wei
Hsu, Fei‐Ting
author_sort Liu, Yu‐Chang
collection PubMed
description Hepatocellular carcinoma (HCC) is recognized as the fifth most common cancer and the third most common cause of death in Asian population. Studies reported that HCC is relatively insensitive to radiotherapy (RT); thus, considering how to sensitize HCC to RT is worth to be elucidated. Epidermal growth factor receptor (EGFR)‐mediated signalling transduction plays the important role in regulating treatment efficacy of HCC. An active compound, 18beta‐glycyrrhetinic acid (18β‐GA), has been reported to own anti‐tumour effect. However, whether 18β‐GA possess RT sensitization ability in HCC remains unclear. Here, we used RNA data from TCGA‐LIHC (Liver hepatocellular carcinoma) to identify the role between EGFR/ERK/nuclear factor kappa B (NF‐κB) signalling and RT by radiosensitivity index (RSI) analysis. We suggested that patients with activated NF‐κB signalling may show resistance to RT treatment, whereas combining 18β‐GA may reinforce RT efficacy in a Hep3B‐bearing animal model. 18β‐GA combined with RT showed superior tumour inhibition capacity as compared to monotherapy and even reached similar efficacy as erlotinib combined with RT. Treatment promotion of RT by 18β‐GA in HCC is not only through diminishing RT‐induced EGFR/ERK/NF‐κB signalling but also promoting RT‐induced apoptosis pathways. 18β‐GA may act as radiosensitizer through inactivating EGFR‐mediated HCC progression and inducing caspase‐dependent apoptosis signalling.
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spelling pubmed-102431612023-06-07 Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma Liu, Yu‐Chang Lin, Cheng Hsun Chen, Kuan‐Tin Lai, De‐Wei Hsu, Fei‐Ting J Cell Mol Med Original Articles Hepatocellular carcinoma (HCC) is recognized as the fifth most common cancer and the third most common cause of death in Asian population. Studies reported that HCC is relatively insensitive to radiotherapy (RT); thus, considering how to sensitize HCC to RT is worth to be elucidated. Epidermal growth factor receptor (EGFR)‐mediated signalling transduction plays the important role in regulating treatment efficacy of HCC. An active compound, 18beta‐glycyrrhetinic acid (18β‐GA), has been reported to own anti‐tumour effect. However, whether 18β‐GA possess RT sensitization ability in HCC remains unclear. Here, we used RNA data from TCGA‐LIHC (Liver hepatocellular carcinoma) to identify the role between EGFR/ERK/nuclear factor kappa B (NF‐κB) signalling and RT by radiosensitivity index (RSI) analysis. We suggested that patients with activated NF‐κB signalling may show resistance to RT treatment, whereas combining 18β‐GA may reinforce RT efficacy in a Hep3B‐bearing animal model. 18β‐GA combined with RT showed superior tumour inhibition capacity as compared to monotherapy and even reached similar efficacy as erlotinib combined with RT. Treatment promotion of RT by 18β‐GA in HCC is not only through diminishing RT‐induced EGFR/ERK/NF‐κB signalling but also promoting RT‐induced apoptosis pathways. 18β‐GA may act as radiosensitizer through inactivating EGFR‐mediated HCC progression and inducing caspase‐dependent apoptosis signalling. John Wiley and Sons Inc. 2023-05-12 /pmc/articles/PMC10243161/ /pubmed/37177859 http://dx.doi.org/10.1111/jcmm.17760 Text en © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Yu‐Chang
Lin, Cheng Hsun
Chen, Kuan‐Tin
Lai, De‐Wei
Hsu, Fei‐Ting
Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
title Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
title_full Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
title_fullStr Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
title_full_unstemmed Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
title_short Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
title_sort inactivation of egfr/erk/nf‐κb signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243161/
https://www.ncbi.nlm.nih.gov/pubmed/37177859
http://dx.doi.org/10.1111/jcmm.17760
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