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Updated: Nov 5, 2025
A Preclinical Murine Model of Hepatic Metastases
Published on: September 27, 2014
Antineoplastic effects of auranofin in human pancreatic adenocarcinoma preclinical models
Mayrim V Rios Perez1, David Roife2, Bingbing Dai3
1Department of General Surgery, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico 00936.
Background:
Auranofin, a Food and Drug Administration-approved anti-rheumatic agent with anticancer properties for lung and ovarian cancer, has never been studied for pancreatic cancer. We hypothesize that auranofin may prevent pancreatic ductal adenocarcinoma progression by inhibition of Txnrd1 and HIF-1α.
Methods:
In vitro sensitivity of human pancreatic ductal adenocarcinoma cell lines was determined based on IC50. Western blot assays were used to interrogate mechanisms of apoptosis and resistance. Ex vivo live tissue slice assays of xenografts allowed for testing of a larger number of PDX samples with high efficiency. In vivo pancreatic ductal adenocarcinoma orthotopic mouse models using MiaPaCa-2 Luc + cells were designed to determine optimal dose and antitumor effect.
Results:
We found that 10 of 15 tested pancreatic ductal adenocarcinoma cell lines were sensitive to auranofin based on IC50s below 5 μmol/L. Ex vivo tissue growth inhibition greater than 44% was observed for 13 PDX tissue cases treated with 10 μmol/L auranofin. High Txnrd1 expression was observed for resistant cell lines. In vivo studies showed 15 mg/kg IP as the optimal dose with absence of gross solid organ metastasis up to 13 weeks post-treatment (median survival 8 and 12 weeks, respectively; P = .0953).
Conclusions:
We have demonstrated that auranofin prevents pancreatic ductal adenocarcinoma progression using multiple models. Our study suggests inhibition of Txnrd1 and HIF-1α as possible mechanisms of action, and Txnrd1 as a biomarker of resistance. Based on these data, an off-label Phase 0 clinical trial with this FDA-approved drug should be considered for patients with pancreatic cancer.
Insights
Auranofin shows promise in preventing pancreatic cancer progression by inhibiting Txnrd1 and HIF-1α. This FDA-approved drug warrants further investigation in clinical trials for pancreatic ductal adenocarcinoma.
Area of Science:
- Oncology
- Drug Discovery
- Cancer Biology
Background:
- Auranofin, an FDA-approved drug for rheumatoid arthritis, exhibits anticancer properties against lung and ovarian cancers.
- Its potential in pancreatic cancer remains unexplored.
- This study investigates auranofin's efficacy and mechanisms in pancreatic ductal adenocarcinoma (PDAC).
Purpose of the Study:
- To evaluate auranofin's effectiveness against pancreatic ductal adenocarcinoma (PDAC) in vitro, ex vivo, and in vivo.
- To explore the underlying mechanisms of action, focusing on Txnrd1 and HIF-1α.
- To identify potential biomarkers for auranofin resistance.
Main Methods:
- Assessed in vitro sensitivity of PDAC cell lines using IC50 values.
- Utilized Western blot to analyze apoptosis and resistance pathways.
- Employed ex vivo live tissue slice assays on patient-derived xenografts (PDX).
- Established in vivo orthotopic mouse models to determine optimal dosing and therapeutic effects.
Main Results:
- 10 out of 15 PDAC cell lines showed sensitivity to auranofin (IC50 < 5 μmol/L).
- Ex vivo assays demonstrated >44% growth inhibition in 13 PDX samples with 10 μmol/L auranofin.
- In vivo studies identified 15 mg/kg IP as optimal dose, significantly reducing metastasis and improving survival.
- High Txnrd1 expression correlated with auranofin resistance.
Conclusions:
- Auranofin effectively prevents pancreatic ductal adenocarcinoma progression across multiple models.
- Inhibition of Txnrd1 and HIF-1α are proposed mechanisms of action.
- Txnrd1 may serve as a predictive biomarker for auranofin resistance.
- An off-label Phase 0 clinical trial for pancreatic cancer patients is recommended.
