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Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells

OBJECTIVES: Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO) therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently,...

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Autores principales: Peng, Hai-Shan, Liao, Ming-Bin, Zhang, Mei-Yin, Xie, Yin, Xu, Li, Zhang, Yao-Jun, Zheng, X. F. Steven, Wang, Hui-Yun, Chen, Yi-Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067386/
https://www.ncbi.nlm.nih.gov/pubmed/24956259
http://dx.doi.org/10.1371/journal.pone.0100814
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author Peng, Hai-Shan
Liao, Ming-Bin
Zhang, Mei-Yin
Xie, Yin
Xu, Li
Zhang, Yao-Jun
Zheng, X. F. Steven
Wang, Hui-Yun
Chen, Yi-Fei
author_facet Peng, Hai-Shan
Liao, Ming-Bin
Zhang, Mei-Yin
Xie, Yin
Xu, Li
Zhang, Yao-Jun
Zheng, X. F. Steven
Wang, Hui-Yun
Chen, Yi-Fei
author_sort Peng, Hai-Shan
collection PubMed
description OBJECTIVES: Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO) therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC) but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells. METHODS: Hepatoma cell lines (BEL-7402 and SK-Hep1) were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR. RESULTS: Although HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation) in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control. CONCLUSIONS: We show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression in hepatoma cells.
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spelling pubmed-40673862014-06-25 Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells Peng, Hai-Shan Liao, Ming-Bin Zhang, Mei-Yin Xie, Yin Xu, Li Zhang, Yao-Jun Zheng, X. F. Steven Wang, Hui-Yun Chen, Yi-Fei PLoS One Research Article OBJECTIVES: Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO) therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC) but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells. METHODS: Hepatoma cell lines (BEL-7402 and SK-Hep1) were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR. RESULTS: Although HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation) in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control. CONCLUSIONS: We show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression in hepatoma cells. Public Library of Science 2014-06-23 /pmc/articles/PMC4067386/ /pubmed/24956259 http://dx.doi.org/10.1371/journal.pone.0100814 Text en © 2014 Peng et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Peng, Hai-Shan
Liao, Ming-Bin
Zhang, Mei-Yin
Xie, Yin
Xu, Li
Zhang, Yao-Jun
Zheng, X. F. Steven
Wang, Hui-Yun
Chen, Yi-Fei
Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells
title Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells
title_full Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells
title_fullStr Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells
title_full_unstemmed Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells
title_short Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells
title_sort synergistic inhibitory effect of hyperbaric oxygen combined with sorafenib on hepatoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067386/
https://www.ncbi.nlm.nih.gov/pubmed/24956259
http://dx.doi.org/10.1371/journal.pone.0100814
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