Related Experiment Video

Updated: Mar 14, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
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Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

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Involvement of DR4/JNK pathway-mediated autophagy in acquired TRAIL resistance in HepG2 cells

Sung-Chul Lim1, Ho Jong Jeon1, Keun Hong Kee1

  • 1Department of Pathology, College of Medicine, Chosun University, Gwangju 61501, Republic of Korea.

International Journal of Oncology
|September 27, 2016
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in cancer cells can be overcome by targeting protective autophagy. This study reveals TRAIL-induced autophagy mediated by DR4 in resistant HepG2 cells, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise as an anticancer agent.
  • TRAIL resistance is a significant challenge in cancer therapy, with mechanisms not fully understood.

Purpose of the Study:

  • To elucidate a novel mechanism of TRAIL resistance in hepatocellular carcinoma cells.
  • To investigate the role of autophagy and DR4 in TRAIL resistance.

Main Methods:

  • Generation of TRAIL-resistant HepG2 cells (HepG2-TR) by exposure to recombinant human TRAIL (rhTRAIL).
  • Assessment of apoptosis and cytotoxicity in response to rhTRAIL.
  • Inhibition of autophagy using 3-methyladenine and ATG5 knockdown.
  • Analysis of DR4 and c-Jun N-terminal kinase involvement.

Main Results:

  • HepG2-TR cells exhibited insensitivity to rhTRAIL and triggered autophagy.
  • Inhibition of autophagy partially restored rhTRAIL-induced apoptosis and cytotoxicity, indicating protective autophagy.
  • rhTRAIL-induced autophagy was mediated by DR4 in HepG2-TR cells, involving c-Jun N-terminal kinase.

Conclusions:

  • A novel mechanism of TRAIL resistance involving DR4-mediated, c-Jun N-terminal kinase-regulated autophagy has been identified.
  • These findings enhance the understanding of TRAIL resistance and suggest potential therapeutic targets.

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