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Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway

Li Li1, Chuting Wang1, Zhenpeng Qiu1

  • 1College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|January 7, 2023
PubMed
Abstract

Insights

Triptolide (TP) effectively inhibits intrahepatic cholangiocarcinoma (ICC) growth by reducing glycolysis through the AKT/mTOR pathway. This study reveals TP as a potential therapeutic agent for ICC, targeting cancer cell proliferation and energy metabolism.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacology

Background:

  • High glycolysis fuels cancer cell proliferation.
  • Triptolide (TP), a natural compound, exhibits anti-cancer properties.
  • The anti-ICC effects and mechanisms of TP remain underexplored.

Purpose of the Study:

  • To investigate the impact of TP on intrahepatic cholangiocarcinoma (ICC) growth.
  • To determine if TP inhibits glycolysis via the AKT/mTOR pathway.

Main Methods:

  • Assessed ICC cell proliferation using CCK-8, clonogenic assays, and flow cytometry.
  • Analyzed glycolysis by measuring glucose/lactate consumption, ATP production, and enzyme activity (HK, PK).
  • Utilized a mouse model with AKT/YapS127A coactivation to evaluate TP's in vivo effects on tumor growth and glycolysis.

Main Results:

  • TP significantly inhibited ICC cell proliferation and glycolysis in a dose- and time-dependent manner.
  • TP suppressed ICC glycolysis by targeting the AKT/mTOR signaling pathway.
  • TP treatment reduced tumor growth and glycolysis in the AKT/YapS127A mouse model.

Conclusions:

  • TP suppresses ICC growth by inhibiting glycolysis via the AKT/mTOR pathway.
  • TP demonstrates potential as a therapeutic agent for ICC treatment.
  • Targeting glycolysis through the AKT/mTOR pathway offers a promising strategy for ICC therapy.
Keywords:
AKT/mTOR pathwayGlycolysisIntrahepatic cholangiocarcinomaProliferationTriptolide

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