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The influence of TNF-α and Ang II on the proliferation, migration and invasion of HepG2 cells by regulating the expression of GRK2

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Abstract

Purpose

Hepatocellular carcinoma (HCC) is a common digestive system malignancy that is associated with a poor prognosis. This study researched the interaction of tumor necrosis factor-α (TNF-α) and angiotensin II (Ang II) in HCC cells proliferation, migration and invasion and examined their influence on the expression of G protein-coupled receptor kinase 2 (GRK2) and relevant receptors.

Methods

Cell Counting Kit-8 and Transwell assays were performed to evaluate the effects of TNF-α and Ang II on HepG2 cells proliferation, migration and invasion. Flow cytometry was used to investigate the expression of tumor necrosis factor receptor 1 (TNFR1), angiotensin II type 1 (AT1R) and type 2 receptors (AT2R) on the surface of HepG2 cells. Additionally, Western blot was performed to assess the modulation of GRK2 expression by TNF-α and Ang II in HepG2 cells. Meanwhile, GRK2 siRNA-transfected HepG2 cells were used to confirm the effects of GRK2, TNF-α and Ang II on the proliferation, migration and invasion of GRK2-knockdown HCC cells. Finally, the expression of TNF-α, Ang II, TNFR1, AT1R, AT2R and GRK2 proteins in HCC, tumor-adjacent and normal liver tissues were tested by immunohistochemistry.

Results

The data demonstrated that TNF-α and Ang II can enhance the proliferation, migration and invasion of HepG2 cells through suppressing GRK2 expression but that the two reagents combined did not have synergistic effects. Moreover,overexpression of TNFR1 and AT1R perhaps promoted the formation and progression of HCC, while high AT2R expression had the opposite effect.

Conclusions

This study provides new ideas for the prevention and treatment of HCC by researching the interaction and probable mechanism of different bioactive factors associated with HCC.

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Acknowledgements

The authors are grateful to the staff members of the Institute of Clinical Pharmacology, Anhui Medical University, for their assistance in conducting the study.

Funding

This study was supported by the Natural Science Foundation of China (Nos. 81330081, 81302784) and the Natural Science Foundation of Anhui Province (No. 1508085MH182).

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, Anhui, People’s Republic of China

    Zhou-wei Xu, Shang-xue Yan, Hua-xun Wu, Jing-yu Chen, Ying Zhang, Ying Li & Wei Wei

  2. Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, People’s Republic of China

    Zhou-wei Xu

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  1. Zhou-wei Xu
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Correspondence to Wei Wei.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Xu, Zw., Yan, Sx., Wu, Hx. et al. The influence of TNF-α and Ang II on the proliferation, migration and invasion of HepG2 cells by regulating the expression of GRK2. Cancer Chemother Pharmacol 79, 747–758 (2017). https://doi.org/10.1007/s00280-017-3267-z

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  • DOI: https://doi.org/10.1007/s00280-017-3267-z

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