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TDF and TAF inhibit liver cancer cell migration, invasion via p7TP3

Jing Zhao1,2, Li Zhou2,3, Yang Zhang2

  • 1Department of Gastoenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, 7 Weiwu Rd, Zhengzhou City, 450003, Henan Province, China.

Scientific Reports
|April 8, 2024
PubMed

Insights

Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) inhibit liver cancer cell growth by downregulating the Wnt/β-catenin pathway and upregulating the tumor suppressor p7TP3. Entecavir (ETV) showed no significant effect.

Area of Science:

  • Hepatology
  • Oncology
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (HCC) is a major complication of chronic Hepatitis B virus (HBV) infection.
  • Tenofovir disoproxil fumarate (TDF) is associated with reduced HCC incidence, but its mechanism is unclear.
  • Investigating TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) mechanisms in liver cancer is crucial.

Purpose of the Study:

  • To elucidate the mechanisms by which TDF, TAF, and ETV affect liver cancer cell malignancy.
  • To explore the role of the Wnt/β-catenin signaling pathway and p7TP3 in TDF/TAF's anti-cancer effects.
  • To compare the efficacy of TDF/TAF with ETV in liver cancer models.

Main Methods:

  • In vitro assays including wound-healing, Transwell invasion, Matrigel Transwell, and CCK-8 to assess cell migration, invasion, and proliferation.
  • TOP/FOP-Flash assay, Western blot, and RT-qPCR to analyze Wnt/β-catenin signaling pathway activity.
  • Quantification of Hepatitis C virus p7 trans-regulated protein 3 (p7TP3) expression in treated liver cancer cells.

Main Results:

  • TDF and TAF significantly inhibited migration, invasion, and proliferation of HepG2 and Huh7 liver cancer cells.
  • TDF/TAF treatment led to decreased Wnt/β-catenin signaling pathway activity.
  • TDF/TAF significantly increased the expression of the tumor suppressor p7TP3 in liver cancer cells, while ETV showed no significant impact.

Conclusions:

  • TDF and TAF demonstrate potential as therapeutic agents for liver cancers, including HCC and hepatoblastoma.
  • The anti-cancer effects of TDF/TAF are mediated through the Wnt/β-catenin signaling pathway.
  • Upregulation of the tumor suppressor p7TP3 is a key mechanism by which TDF/TAF exert their effects.
Keywords:
Liver cancersTDF/TAFWnt/β-cateninp7TP3

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