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Adiponectin Receptor Agonist Effectively Suppresses Hepatocellular Carcinoma Growth

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Abstract

Hepatocellular carcinoma (HCC) is the second lethal cancer. Short overall survival, low five-year survival rate, and unimproved treatment efficacy urge the need to improve HCC prognosis. Adiponectin is key protector against cancer and hepatic abnormalities. Hypoadiponectinemia occurs in and promotes carcinogenesis and hepatic diseases. Adiponectin reactivation by different methods showed impressive effect against cancer and hepatic diseases. Recently, AdipoRon, an adiponectin receptor agonist, can interact with both Adiponectin receptors. AdipoRon showed promising anti-cancer effect in some cancers, but no study on HCC yet. The in vitro effect of AdipoRon on HCC was investigated by cell viability, migration, invasion, colony formation and apoptosis assays. The signalling alteration was determined by RT-qPCR and Western blot. The effect of treatment was interpreted by comparison between treatments and control. The difference between two cell lines was relatively compared. Our results showed significant in vitro anti-cancer effect of AdipoRon via AMPK- and dose-dependent manner. Huh7 cells showed a lower level of AdipoR1/2 and a superior proliferation and aggressiveness, compared to Hep3B. In addition, Huh7 cells were more sensitive to AdipoRon treatment (lower IC50, less cell growth, migration, invasion and colonies upon AdipoRon treatment) than Hep3B cells. In conclusion, AdipoRon effectively inhibited HCC growth and invasiveness in vitro. The deficient expression of adiponectin receptors affects efficacy of AdipoRon and aggressiveness of HCC cells.

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Data Availability

The datasets generated during and/or analysed during the current study are not publicly available due to the management policy but are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the Department of equipment and material supplies, Vietnam Military Medical University for their support.

Funding

Thi Mai Ly Nguyen was funded by Vingroup JSC and supported by the Postdoctoral Scholarship Programme of Vingroup Innovation Foundation (VINIF), Institute of Big Data, code VINIF.2021.STS.25”. This research is funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number 108.02-2019.324. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Vietnam Military Medical University, Hanoi, Vietnam

    Mai Ly Thi Nguyen, Van Tran Pham, Ba Thang Ta, Dinh Tuan Le, Quoc Vuong Le, Xuan Cuong Hoang, Linh Toan Nguyen & Khac Cuong Bui

  2. Department of Biochemistry, Military Hospital 103, Hanoi, Vietnam

    Mai Ly Thi Nguyen & Van Tran Pham

  3. Laboratory Animal Research Centre, Vietnam Military Medical University, Hanoi, Vietnam

    Chi Pham, Phuong Linh Thi Nham & Khac Cuong Bui

  4. Respiratory Centre, Military Hospital 103, Hanoi, Vietnam

    Ba Thang Ta

  5. Department of Rheumatology and Endocrinology, Military Hospital 103, Hanoi, Vietnam

    Dinh Tuan Le

  6. Department of Medical Examination, Le Huu Trac National Burn Hospital, Hanoi, Vietnam

    Quoc Vuong Le

  7. Department of Internal medicine I, Universitätsklinikum Tübingen, Tübingen, Germany

    Przemyslaw Bozko & Khac Cuong Bui

  8. The M3 Research Institute, Tübingen, Germany

    Przemyslaw Bozko

  9. Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam

    Linh Toan Nguyen & Khac Cuong Bui

  10. Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam

    Linh Toan Nguyen & Khac Cuong Bui

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  1. Mai Ly Thi Nguyen
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Contributions

K.C.B., L.T.N. and M.L.T.N. designed the study and acquired the fund. K.C.B., P.B. and M.L.T.N. interpreted data and drafted manuscript. V.T.P. and B.T.T. provide technical and ideal consultant. M.L.T.N., C.P. and P.L.T.N. performed experiments. Q.V.L., X.C.H. and D.T.L. revised data analysis. All authors reviewed and approved the final version of manuscript.

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Correspondence to Khac Cuong Bui.

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Nguyen, M.L.T., Pham, C., Pham, V.T. et al. Adiponectin Receptor Agonist Effectively Suppresses Hepatocellular Carcinoma Growth. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01217-9

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