Title:Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-like Cell (CCSLCs) Properties
Volume: 20
Issue: 1
Author(s): Nasim Alamdar, Shirin Farivar, Kaveh Baghaei, Amir Ali Hamidieh, Hossein Soltaninejad, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali and Zohreh Saltanatpour*
Affiliation:
- Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Cancer stem cells (CSCs), EMT, colon cancer stem cell, pioglitazone, cetuximab, CSC targeting drugs, EMT targeting drugs.
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.
