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Hydrogen sulfide suppresses H2O2-induced proliferation and migration of HepG2 cells through Wnt/β-catenin signaling pathway

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Abstract

Both H2S and H2O2 affect many cellular events, such as cell differentiation, cell proliferation and cell death. However, there is some controversy about the roles of H2S and H2O2, since the detailed mechanisms they are involved remain unclear. In this study, low concentration of H2O2 (40 μM) increased the viability of hepatocellular carcinoma cells HepG2, while both H2S and high concentration of H2O2 decreased the cell viability in a dose-dependent manner. Wound healing assay indicated that 40 μM H2O2 promoted migration of HepG2 cells, which was suppressed by exogenous H2S. Further analysis revealed that administration of exogenous H2S and H2O2 changed the redox status of Wnt3a in HepG2 cells. Altered expression of proteins including Cyclin D1, TCF-4, and MMP7, which are downstream of the Wnt3a/β-catenin signaling pathway, were found after treatment with exogenous H2S and H2O2. Compared with H2S, low concentration of H2O2 showed opposite effects on these protein expression levels in HepG2 cells. These results suggest that H2S suppressed H2O2-induced proliferation and migration of HepG2 through regulating Wnt3a/β-catenin signaling pathway.

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Data availability

All data is openly available in the public database. The data that support the findings of this study are openly available in the Cancer Genome Atlas (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and Genotype-Tissue Expression (https://www.gtexportal.org/home).

Abbreviations

HCC:

Hepatocellular carcinoma

H2S:

Hydrogen sulfide

RFA:

Radiofrequency ablation

TACE:

Transcatheter arterial chemoembolization

JAK:

Janus protein tyrosine kinase

CCK-8:

Cell counting kit

NO:

Nitric oxide

CO:

Carbon monoxide

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Acknowledgements

This work was supported by The Chongqing Natural Science Foundation Project (No. CSTC2020jcyj- msxmX0912) and the Yuzhong District Basic Research and Frontier Exploration Project of Chongqing (No. 20200136). We also thank Dr. Xunling Han for help with pathological examinations.

Funding

This study was funded by The Chongqing Natural Science Foundation Project, CSTC2020jcyj- msxmX0912, Hongzhi Zhao, Yuzhong District Basic Research and Frontier Exploration Project of Chongqing, 20200136, Hongzhi Zhao

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Chongqing Emergency Medical Center, Chongqing, 400014, China

    Hongzhi Zhao, Liang Zhao, Lin Wu, Sheng Hu, Yangmei Huang & Wei Zhao

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  1. Hongzhi Zhao
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  2. Liang Zhao
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  3. Lin Wu
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  4. Sheng Hu
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Contributions

ZH designed the study. ZH performed the experiments and analyzed the data, with assistance from ZL, WL and HS. ZW analyzed the data. ZH wrote the manuscript which was read and revised by all authors read.

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Correspondence to Hongzhi Zhao.

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Zhao, H., Zhao, L., Wu, L. et al. Hydrogen sulfide suppresses H2O2-induced proliferation and migration of HepG2 cells through Wnt/β-catenin signaling pathway. Med Oncol 40, 214 (2023). https://doi.org/10.1007/s12032-023-02091-w

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