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Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-Like Cell (Ccslcs) Properties Publisher Pubmed



Alamdar N1 ; Farivar S1 ; Baghaei K2, 3 ; Hamidieh AA4, 5 ; Soltaninejad H6 ; Aghdaei HA2, 3 ; Zali MR3 ; Saltanatpour Z4
Authors
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Authors Affiliations
  1. 1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
  2. 2. Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Tehran, Iran
  3. 3. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Pediatric Cell and Gene Therapy Research Center, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Gene, Tehran, Iran
  5. 5. Stem Cell and Regenerative Medicine Innovation Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Tehran, Iran

Source: Current stem cell research & therapy Published:2025


Abstract

BACKGROUND: One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named HT29-shE. In the present study, these cells were used to investigate the effect of Pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents. METHODS: The viability and IC50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring. RESULTS: The findings showed that Pio and Cet at concentrations of 250 μM and 40 μg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal- toepithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment. CONCLUSION: Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.