Helicobacter pylori-Derived Outer Membrane Vesicles Promote Hepatocellular Carcinoma Cell Proliferation with PI3K/AKT/mTOR Activation and Cyclin D1 Upregulation
- 1Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
- 2Laboratory of Infectious and Liver Diseases, Institution of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
- 3Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China
Abstract
Accumulating evidence suggests an association between Helicobacter pylori infection and liver diseases; however, it remains unclear whether H. pylori or its extracellular products directly influence hepatocellular carcinoma (HCC) biology. Here, we examined the effects of viable H. pylori, sterile H. pylori-conditioned supernatant (Hp-CS), and isolated H. pylori-derived outer membrane vesicles (Hp-OMVs) on HCC cells. H. pylori adhered to and invaded Huh7 and Hepa1-6 cells, increased Cyclin D1 expression, and enhanced the growth of tumors derived from bacteria-exposed Hepa1-6 cells in immunocompetent C57BL/6J mice. Hp-CS increased HCC cell metabolic activity, colony formation, migration, and invasion. Hp-OMVs were characterized by transmission electron microscopy and nanoparticle tracking analysis. Exposure to Hp-OMVs increased HCC cell metabolic activity, colony formation, cell-cycle progression, and tumor growth in a syngeneic mouse model. Hp-OMVs also increased PI3K, AKT, and mTOR phosphorylation and elevated Cyclin D1 expression. The PI3K inhibitor LY294002 attenuated these molecular changes and reduced Hp-OMV-induced cell-cycle progression and colony formation. These findings show that H. pylori and its extracellular products promote proliferation-associated phenotypes in experimental HCC models. Hp-OMVs are biologically active extracellular components of H. pylori, and pharmacological inhibition supports the involvement of PI3K/AKT/mTOR signaling and Cyclin D1 upregulation in their growth-promoting effects.
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BibTeX
@article{zhou2026helicobacter,
title = {{Helicobacter pylori-Derived Outer Membrane Vesicles Promote Hepatocellular Carcinoma Cell Proliferation with PI3K/AKT/mTOR Activation and Cyclin D1 Upregulation}},
author = {Jun-Peng Zhou and Xiao-Na Song and Jiao Li and Hui Huang and Han Chen and Hong Tang and Hong Li},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219573},
url = {https://www.mdpi.com/1422-0067/27/21/9573},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Helicobacter pylori-Derived Outer Membrane Vesicles Promote Hepatocellular Carcinoma Cell Proliferation with PI3K/AKT/mTOR Activation and Cyclin D1 Upregulation
AU - Jun-Peng Zhou
AU - Xiao-Na Song
AU - Jiao Li
AU - Hui Huang
AU - Han Chen
AU - Hong Tang
AU - Hong Li
PY - 2026
DA - 2026/10/26
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219573
UR - https://www.mdpi.com/1422-0067/27/21/9573
AB - Accumulating evidence suggests an association between Helicobacter pylori infection and liver diseases; however, it remains unclear whether H. pylori or its extracellular products directly influence hepatocellular carcinoma (HCC) biology. Here, we examined the effects of viable H. pylori, sterile H. pylori-conditioned supernatant (Hp-CS), and isolated H. pylori-derived outer membrane vesicles (Hp-OMVs) on HCC cells. H. pylori adhered to and invaded Huh7 and Hepa1-6 cells, increased Cyclin D1 expression, and enhanced the growth of tumors derived from bacteria-exposed Hepa1-6 cells in immunocompetent C57BL/6J mice. Hp-CS increased HCC cell metabolic activity, colony formation, migration, and invasion. Hp-OMVs were characterized by transmission electron microscopy and nanoparticle tracking analysis. Exposure to Hp-OMVs increased HCC cell metabolic activity, colony formation, cell-cycle progression, and tumor growth in a syngeneic mouse model. Hp-OMVs also increased PI3K, AKT, and mTOR phosphorylation and elevated Cyclin D1 expression. The PI3K inhibitor LY294002 attenuated these molecular changes and reduced Hp-OMV-induced cell-cycle progression and colony formation. These findings show that H. pylori and its extracellular products promote proliferation-associated phenotypes in experimental HCC models. Hp-OMVs are biologically active extracellular components of H. pylori, and pharmacological inhibition supports the involvement of PI3K/AKT/mTOR signaling and Cyclin D1 upregulation in their growth-promoting effects.
SN - 1422-0067
ER -