Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways

Abstract Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there are several controversies concerning the role of H2S in cancer development and progression. In this study, we found that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10–100...

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Autores principales: Dongdong Wu, Mengling Li, Wenke Tian, Shuaiwei Wang, Longzhen Cui, Hui Li, Huijuan Wang, Ailing Ji, Yanzhang Li
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/3727773a682c42a9b1f409125cfc76a3
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spelling oai:doaj.org-article:3727773a682c42a9b1f409125cfc76a32021-12-02T15:05:46ZHydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways10.1038/s41598-017-05457-z2045-2322https://doaj.org/article/3727773a682c42a9b1f409125cfc76a32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05457-zhttps://doaj.org/toc/2045-2322Abstract Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there are several controversies concerning the role of H2S in cancer development and progression. In this study, we found that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10–100 μM NaHS and dose-dependently inhibited by 600–1000 μM NaHS. The apoptotic levels were reduced by 25–100 μM NaHS but increased by 400–1000 μM NaHS in HCC cells. After treatment with 25–50 μM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down-regulated. Administration of 800–1000 μM NaHS showed opposite effects on these protein levels in HCC cells. However, H2S showed no effects on the growth, migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways in L02 cells. Furthermore, 25–100 μM NaHS promoted HCC tumor growth and blood vessel formation, while 800–1000 μM NaHS inhibited angiogenesis and tumor growth with no obvious systemic toxicity. These results indicate that H2S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Novel H2S donors could be designed and applied for further antitumor research.Dongdong WuMengling LiWenke TianShuaiwei WangLongzhen CuiHui LiHuijuan WangAiling JiYanzhang LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Dongdong Wu
Mengling Li
Wenke Tian
Shuaiwei Wang
Longzhen Cui
Hui Li
Huijuan Wang
Ailing Ji
Yanzhang Li
Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways
description Abstract Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there are several controversies concerning the role of H2S in cancer development and progression. In this study, we found that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10–100 μM NaHS and dose-dependently inhibited by 600–1000 μM NaHS. The apoptotic levels were reduced by 25–100 μM NaHS but increased by 400–1000 μM NaHS in HCC cells. After treatment with 25–50 μM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down-regulated. Administration of 800–1000 μM NaHS showed opposite effects on these protein levels in HCC cells. However, H2S showed no effects on the growth, migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways in L02 cells. Furthermore, 25–100 μM NaHS promoted HCC tumor growth and blood vessel formation, while 800–1000 μM NaHS inhibited angiogenesis and tumor growth with no obvious systemic toxicity. These results indicate that H2S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Novel H2S donors could be designed and applied for further antitumor research.
format article
author Dongdong Wu
Mengling Li
Wenke Tian
Shuaiwei Wang
Longzhen Cui
Hui Li
Huijuan Wang
Ailing Ji
Yanzhang Li
author_facet Dongdong Wu
Mengling Li
Wenke Tian
Shuaiwei Wang
Longzhen Cui
Hui Li
Huijuan Wang
Ailing Ji
Yanzhang Li
author_sort Dongdong Wu
title Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways
title_short Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways
title_full Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways
title_fullStr Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways
title_full_unstemmed Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways
title_sort hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through egfr/erk/mmp-2 and pten/akt signaling pathways
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3727773a682c42a9b1f409125cfc76a3
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