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Updated: Jan 29, 2026
Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer
Published on: July 18, 2017
Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model
Johannes Klose1, Stefan Trefz1, Tobias Wagner1
1Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Objectives:
Salinomycin is a polyether antibiotic with selective activity against human cancer stem cells. The impact of salinomycin on patient-derived primary human colorectal cancer cells has not been investigated so far. Thus, here we aimed to investigate the activity of salinomycin against tumor initiating cells isolated from patients with colorectal cancer.
Methods:
Primary tumor-initiating cells (TIC) isolated from human patients with colorectal liver metastases or from human primary colon carcinoma were exposed to salinomycin and compared to treatment with 5-FU and oxaliplatin. TICs were injected subcutaneously into NOD/SCID mice to induce a patient-derived mouse xenograft model of colorectal cancer. Animals were treated either with salinomycin, FOLFOX regimen, or salinomycin and FOLFOX. Human colorectal cancer cells were used to delineate an underlying molecular mechanism of salinomycin in this tumor entity.
Results:
Applying TICs isolated from human patients with colorectal liver metastases or from human primary colon carcinoma, we demonstrated that salinomycin exerts increased antiproliferative activity compared to 5-fluorouracil and oxaliplatin treatment. Consistently, salinomycin alone or in combination with FOLFOX exerts superior antitumor activity compared to FOLFOX therapy in a patient-derived mouse xenograft model of colorectal cancer. Salinomycin induces apoptosis of human colorectal cancer cells, accompanied by accumulation of dysfunctional mitochondria and reactive oxygen species. These effects are associated with expressional down-regulation of superoxide dismutase-1 (SOD1) in response to salinomycin treatment.
Conclusion:
Collectively, the results of this pre-clinical study indicate that salinomycin alone or in combination with 5-fluorouracil and oxaliplatin exerts increased antitumoral activity compared to common chemotherapy.
Insights
Salinomycin shows greater effectiveness against colorectal cancer stem cells than standard chemotherapy. This preclinical study suggests salinomycin, alone or combined with FOLFOX, offers superior antitumor activity.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Salinomycin, a polyether antibiotic, exhibits selective activity against cancer stem cells.
- The efficacy of salinomycin in patient-derived colorectal cancer cells remains unexplored.
Purpose of the Study:
- To investigate the activity of salinomycin against tumor-initiating cells (TICs) from human colorectal cancer patients.
- To compare salinomycin's efficacy with standard chemotherapy (5-FU and oxaliplatin).
Main Methods:
- Patient-derived TICs from colorectal liver metastases and primary colon carcinoma were treated with salinomycin, 5-FU, and oxaliplatin.
- A patient-derived mouse xenograft model was established using TICs.
- Mice were treated with salinomycin, FOLFOX, or a combination of both.
Main Results:
- Salinomycin demonstrated superior antiproliferative activity against colorectal TICs compared to 5-FU and oxaliplatin.
- Salinomycin, alone or with FOLFOX, showed enhanced antitumor activity in xenograft models versus FOLFOX alone.
- Salinomycin induced apoptosis, mitochondrial dysfunction, and reactive oxygen species accumulation, linked to SOD1 downregulation.
Conclusions:
- Salinomycin exhibits significant preclinical antitumoral activity in colorectal cancer.
- Salinomycin, alone or combined with 5-FU and oxaliplatin, is more effective than current chemotherapy regimens.
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