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PP-63

Triptolide induces cell injury and chemosensitivity through regulation of

CARMA3 expression and ROS accumulation in hepatocellular carcinoma

,3
1
Chih-Yang Huang, Tung-Wei Hsu, Po-Hsiang Liao*
2

1 Cardiovascular and Mitochondria Related Disease Research Center, Hualien Tzu Chi
Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan
2 Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical
University, New Taipei City 23561, Taiwan
3 Center for Drug Research and Development, College of Human Ecology, Chang Gung
University of Science and Technology, Taoyuan, 333324, Taiwan.
* E-mail: phliao@mail.cgust.edu.tw

Abstract
Triptolide, a diterpenoid triepoxide isolated from the traditional Chinese herb Tripterygium
wilfordii, has been reported to exhibit potent anti-inflammatory and anti-cancer activities in
multiple malignancies. Hepatocellular carcinoma (HCC), the most common primary liver
cancer and the second leading cause of cancer-related mortality, remains difficult to treat due
to its heterogeneity and limited therapeutic options. Sorafenib, a multi-kinase inhibitor and the
standard first-line systemic therapy for advanced HCC, offers only modest survival benefits
and often leads to acquired resistance with prolonged administration. Identifying the molecular
mechanisms underlying drug resistance is therefore critical for developing improved treatments.
CARMA3 (CARD10), a membrane-associated scaffold protein, has recently emerged as an
important oncogenic regulator in solid tumors. In this study, we show that CARMA3
contributes to chemoresistance in HCC, while triptolide enhances chemosensitivity by
downregulating CARMA3 expression and promoting reactive oxygen species (ROS)
accumulation. These findings suggest that triptolide acts as a chemosensitizing agent through
the modulation of CARMA3-mediated ROS production and ferroptosis resistance, providing a
novel therapeutic strategy for overcoming drug resistance in HCC.

Keywords: Triptolide; CARMA3; Hepatocellular carcinoma; Sorafenib; Chemoresistance