Related Experiment Video
Updated: May 2, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by
Abstract:
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies characterized by an intense tumor stroma with hypoperfused regions, a significant inflammatory response and pronounced therapy resistance. New therapeutic agents are urgently needed. The plant-derived agent triptolide also known as "thunder god vine" has a long history in traditional Chinese medicine for treatment of rheumatoid arthritis and cancer and is now in a clinical phase II trial for establishing the efficacy against a placebo. The authors mimicked the situation in patient tumors by induction of hypoxia in experimental models of pancreatic cancer stem cells (CSCs) and evaluated the therapeutic effect of triptolide. Hypoxia led to induction of colony and spheroid formation, aldehyde dehydrogenase 1 (ALDH1) and NF-κB activity, migratory potential and a switch in morphology to a fibroblastoid phenotype, as well as stem cell- and epithelial-mesenchymal transition-associated protein expression. Triptolide efficiently inhibited hypoxia-induced transcriptional signaling and downregulated epithelial-mesenchymal transition (EMT) and CSC features in established highly malignant cell lines, whereas sensitive cancer cells or nonmalignant cells were less affected. In vivo triptolide inhibited tumor take and tumor growth. In primary CSCs isolated from patient tumors, triptolide downregulated markers of CSCs, proliferation and mesenchymal cells along with upregulation of markers for apoptosis and epithelial cells. This study is the first to show that triptolide reverses EMT and CSC characteristics and therefore may be superior to current chemotherapeutics for treatment of PDA.
Insights
Triptolide, a plant-derived compound, effectively reversed cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT) features in pancreatic ductal adenocarcinoma models. This suggests triptolide may offer a superior therapeutic strategy for this lethal cancer.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with significant therapeutic resistance.
- Tumor microenvironments in PDA are characterized by hypoxia, inflammation, and a dense stroma.
- Novel therapeutic agents are urgently needed to overcome treatment resistance in PDA.
Purpose of the Study:
- To evaluate the therapeutic potential of triptolide, a plant-derived agent, against pancreatic cancer stem cells (CSCs) under hypoxic conditions.
- To investigate triptolide's effects on epithelial-mesenchymal transition (EMT) and CSC characteristics in PDA models.
- To determine if triptolide can reverse established malignant phenotypes in PDA.
Main Methods:
- Induction of hypoxia in experimental models of pancreatic cancer stem cells (CSCs).
- Treatment with triptolide and evaluation of its effects on CSC markers, EMT markers, proliferation, apoptosis, and cell morphology.
- In vivo studies to assess triptolide's impact on tumor growth and development.
- Analysis of primary CSCs isolated from patient tumors.
Main Results:
- Hypoxia induced CSC features, EMT, and migratory potential in pancreatic cancer cells.
- Triptolide significantly inhibited hypoxia-induced signaling, downregulating EMT and CSC characteristics in malignant cell lines.
- Triptolide demonstrated efficacy in vivo, inhibiting tumor take and growth.
- In primary patient-derived CSCs, triptolide reversed CSC and mesenchymal markers while promoting apoptosis and epithelial markers.
Conclusions:
- Triptolide effectively reverses hypoxia-induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) characteristics in pancreatic ductal adenocarcinoma.
- Triptolide exhibits therapeutic potential by targeting key pathways driving PDA malignancy and resistance.
- This study suggests triptolide may be a promising therapeutic agent for PDA, potentially outperforming current chemotherapeutics.
