Aucubin Inhibits Liver Cancer via HMGB1-mediated Inactivation of the PI3K/AKT/mTOR Signaling Pathway

Weinan Li1,2, Xuan Ma3, Yong Mei1

  • 1Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550001, China.

Abstract

Insights

Aucubin, a natural compound, effectively suppresses liver cancer by inhibiting cell migration and invasion. It targets the HMGB1/RAGE axis and PI3K/AKT/mTOR pathway, showing potential as a novel liver cancer therapeutic.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Liver cancer is a lethal malignancy with limited treatment options.
  • Previous research indicated aucubin's role in attenuating liver injury via the HMGB1/TLR-4/NF-κB pathway.
  • This study investigates aucubin's function and mechanisms in liver cancer.

Purpose of the Study:

  • To elucidate the anti-tumor effects and molecular mechanisms of aucubin in liver cancer.
  • To determine if aucubin's anti-cancer activity is mediated by the HMGB1 signaling pathway.
  • To explore the potential of aucubin as a therapeutic agent for liver cancer.

Main Methods:

  • Utilized liver cancer cell and tumor-bearing mouse models to assess aucubin's anti-tumor effects.
  • Investigated the dependency of aucubin's efficacy on HMGB1 and associated signaling pathways.
  • Analyzed protein expression levels, including HMGB1, RAGE, p-PI3K, p-AKT, and p-mTOR.

Main Results:

  • Aucubin inhibited epithelial-mesenchymal transition, migration, and invasion of liver cancer cells in vivo and in vitro.
  • Overexpression of HMGB1 reversed the inhibitory effects of aucubin on migration and proliferation.
  • Aucubin decreased HMGB1, RAGE, p-PI3K, p-AKT, and p-mTOR protein levels, which was reversed by HMGB1 overexpression.

Conclusions:

  • Aucubin exerts anti-liver cancer effects by upregulating the HMGB1/RAGE axis.
  • Aucubin targets the PI3K/AKT/mTOR pathway to inhibit liver cancer proliferation, invasion, and metastasis.
  • Aucubin demonstrates significant potential as a therapeutic agent for liver cancer treatment.

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