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Updated: Oct 23, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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TDO2 Was Downregulated in Hepatocellular Carcinoma and Inhibited Cell Proliferation by Upregulating the Expression of

Chengpeng Yu1,2, Dean Rao1,2, He Zhu1,2

  • 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Biomed Research International
|August 23, 2021
PubMed
Abstract

Insights

Low expression of tryptophan-2,3-dioxygenase (TDO2) in hepatocellular carcinoma (HCC) correlates with poor prognosis. TDO2 restrains HCC cell growth and induces cell-cycle arrest, indicating its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Tryptophan-2,3-dioxygenase (TDO2) catalyzes the rate-limiting step in the kynurenine pathway.
  • TDO2 overexpression is observed in various human cancers.
  • The specific role of TDO2 in hepatocellular carcinoma (HCC) remains debated.

Purpose of the Study:

  • To investigate the role of TDO2 in hepatocellular carcinoma (HCC).
  • To determine the prognostic significance of TDO2 expression in HCC.
  • To explore TDO2 as a potential therapeutic target for HCC.

Main Methods:

  • Western blot and immunochemistry to assess TDO2 expression in human HCC tissues.
  • In vitro assays (CCK8, colony formation) to evaluate TDO2's effect on HCC cell proliferation.
  • In vivo xenograft mouse model to assess TDO2's impact on tumor growth.
  • Flow cytometry to analyze cell cycle status.

Main Results:

  • Reduced TDO2 expression was observed in HCC tissues.
  • Low TDO2 expression was significantly associated with poor prognosis and adverse clinical outcomes.
  • TDO2 demonstrated inhibitory effects on HCC cell proliferation both in vitro and in vivo.
  • TDO2 upregulated p21 and p27 expression, leading to cell-cycle arrest.

Conclusions:

  • Loss of TDO2 expression in HCC is linked to unfavorable prognosis.
  • TDO2 exhibits tumor-suppressive functions in HCC.
  • TDO2 represents a promising biomarker and therapeutic target for hepatocellular carcinoma.

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