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Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression
BACKGROUND: HBV promotes cell survival by upregulating the expression of the cellular inhibitor of apoptosis protein 2 (cIAP2), however whether it is involved in HBV-induced sorafenib resistance in liver cancer remains unclear. METHODS: cIAP2 overexpression and knockdown was adopted to assess the in...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988944/ https://www.ncbi.nlm.nih.gov/pubmed/33757557 http://dx.doi.org/10.1186/s13027-021-00359-2 |
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author | Zhang, Shouhua Li, Nuoya Sheng, Yanling Chen, Wen Ma, Qiangliang Yu, Xin Lian, Jianping Zeng, Junquan Yang, Yipeng Yan, Jinlong |
author_facet | Zhang, Shouhua Li, Nuoya Sheng, Yanling Chen, Wen Ma, Qiangliang Yu, Xin Lian, Jianping Zeng, Junquan Yang, Yipeng Yan, Jinlong |
author_sort | Zhang, Shouhua |
collection | PubMed |
description | BACKGROUND: HBV promotes cell survival by upregulating the expression of the cellular inhibitor of apoptosis protein 2 (cIAP2), however whether it is involved in HBV-induced sorafenib resistance in liver cancer remains unclear. METHODS: cIAP2 overexpression and knockdown was adopted to assess the involvement of cIAP2 in HBV-induced sorafenib resistance. Anti-HBV drug lamivudine and Akt inhibitor were used to investigate the impact of HBV replication on cIAP2 expression and sorafenib resistance. Xenotransplantation mouse model was used to confirm the data on cell lines in vitro. RESULTS: Liver cancer cell line HepG2.215 showed increased cIAP2 expression and enhanced resistance to sorafenib. Upon sorafenib treatment, overexpression of cIAP2 in HepG2 lead to decreased cleaved caspase 3 level and increased cell viability, while knockdown of cIAP2 in HepG2.215 resulted in increased level of cleaved caspase 3 and decreased cell viability, suggesting the involvement of cIAP2 in HBV-induced sorafenib resistance. Furthermore, anti-HBV treatment reduced cIAP2 expression and partially restored sorafenib sensitivity in HepG2.215 cells. Xenotransplantation mouse model further confirmed that co-treatment with lamivudine and sorafenib could reduce sorafenib-resistant HepG2.215 tumor cell growth. CONCLUSION: cIAP2 is involved in HBV-induced sorafenib resistance in liver cancer and anti-HBV treatments reduce cIAP2 expression and partially restore sorafenib sensibility. |
format | Online Article Text |
id | pubmed-7988944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79889442021-03-25 Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression Zhang, Shouhua Li, Nuoya Sheng, Yanling Chen, Wen Ma, Qiangliang Yu, Xin Lian, Jianping Zeng, Junquan Yang, Yipeng Yan, Jinlong Infect Agent Cancer Research Article BACKGROUND: HBV promotes cell survival by upregulating the expression of the cellular inhibitor of apoptosis protein 2 (cIAP2), however whether it is involved in HBV-induced sorafenib resistance in liver cancer remains unclear. METHODS: cIAP2 overexpression and knockdown was adopted to assess the involvement of cIAP2 in HBV-induced sorafenib resistance. Anti-HBV drug lamivudine and Akt inhibitor were used to investigate the impact of HBV replication on cIAP2 expression and sorafenib resistance. Xenotransplantation mouse model was used to confirm the data on cell lines in vitro. RESULTS: Liver cancer cell line HepG2.215 showed increased cIAP2 expression and enhanced resistance to sorafenib. Upon sorafenib treatment, overexpression of cIAP2 in HepG2 lead to decreased cleaved caspase 3 level and increased cell viability, while knockdown of cIAP2 in HepG2.215 resulted in increased level of cleaved caspase 3 and decreased cell viability, suggesting the involvement of cIAP2 in HBV-induced sorafenib resistance. Furthermore, anti-HBV treatment reduced cIAP2 expression and partially restored sorafenib sensitivity in HepG2.215 cells. Xenotransplantation mouse model further confirmed that co-treatment with lamivudine and sorafenib could reduce sorafenib-resistant HepG2.215 tumor cell growth. CONCLUSION: cIAP2 is involved in HBV-induced sorafenib resistance in liver cancer and anti-HBV treatments reduce cIAP2 expression and partially restore sorafenib sensibility. BioMed Central 2021-03-23 /pmc/articles/PMC7988944/ /pubmed/33757557 http://dx.doi.org/10.1186/s13027-021-00359-2 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Zhang, Shouhua Li, Nuoya Sheng, Yanling Chen, Wen Ma, Qiangliang Yu, Xin Lian, Jianping Zeng, Junquan Yang, Yipeng Yan, Jinlong Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression |
title | Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression |
title_full | Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression |
title_fullStr | Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression |
title_full_unstemmed | Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression |
title_short | Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression |
title_sort | hepatitis b virus induces sorafenib resistance in liver cancer via upregulation of ciap2 expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988944/ https://www.ncbi.nlm.nih.gov/pubmed/33757557 http://dx.doi.org/10.1186/s13027-021-00359-2 |
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