Related Experiment Video

Updated: Jan 11, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Disrupting CARMA3 Signaling with Triptolide Reverses Sorafenib Resistance in Hepatocellular Carcinoma

Wan-Yu Wang1, Tung-Wei Hsu1,2, Yen-Hao Su1,3,4,5,6,7

  • 1Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan.

International Journal of Medical Sciences
|November 10, 2025
PubMed

Insights

Triptolide overcomes liver cancer drug resistance by targeting CARMA3. This enhances chemotherapy effectiveness by promoting cell death pathways and reactive oxygen species accumulation.

Area of Science:

  • Hepatocellular carcinoma (HCC) research
  • Cancer drug resistance mechanisms
  • Molecular oncology

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent liver cancer with limited treatment options.
  • Sorafenib, a first-line therapy for advanced HCC, provides minimal survival benefits and often leads to drug resistance.
  • Understanding the molecular basis of HCC drug resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of CARMA3 (CARD10) in HCC chemoresistance.
  • To explore the potential of triptolide as a chemosensitizing agent in HCC.
  • To elucidate the molecular mechanisms by which triptolide overcomes drug resistance.

Main Methods:

  • Investigated CARMA3 expression and its role in HCC chemoresistance.
  • Assessed the effect of triptolide on HCC cell sensitivity to chemotherapy.
  • Analyzed triptolide's impact on CARMA3 expression, reactive oxygen species (ROS) levels, and ferroptosis.

Main Results:

  • CARMA3 was found to contribute to chemoresistance in hepatocellular carcinoma.
  • Triptolide demonstrated the ability to enhance chemosensitivity in HCC models.
  • Triptolide treatment led to decreased CARMA3 expression and increased ROS accumulation, sensitizing cells to ferroptosis.

Conclusions:

  • CARMA3 plays a significant role in mediating chemoresistance in HCC.
  • Triptolide acts as a chemosensitizing agent by downregulating CARMA3 and inducing ROS accumulation.
  • Targeting CARMA3 and modulating ROS/ferroptosis presents a novel therapeutic strategy for overcoming HCC drug resistance.
Keywords:
CARMA3chemoresistancehepatocellular carcinomasorafenibtriptolide

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