Study of the effect of Pioglitazone and Cetuximab on Cancer Stem-like Cellsenriched HT29 cell line

Abstract One of the major causes of cancer resistance to chemotherapy has been found to be the presence of Cancer Stem Cells (CSCs) in cancerous tissues. Probably, these cells are the source of cancer and the cause of malignancy and recurrence in the affected population. Therefore, it is possible to target CSCs to treat cancer. Since the percentage of CSCs in the total tumor mass is very low, so studies about these cells depend on their isolation and enrichment methods. Some studies have suggested that EMT induction in population of normal epithelial cells and cancer cells by inhibiting of E-cadherin, protects them against chemotherapy, anticancer and apoptosis drugs, moreover they get characteristics of CSCs. So in order to study CSCs can enrich them by inhibiting of E-cadherin in tumor population.In this study, we tried to examine how the effect of Pioglitazone and Cetuximab, two drugs used in chemotherapy of Colon Cancer, on CSCs enriched HT29 cell line (was called HT29-shE) in which CSCs were enriched with induction of EMT by inhibiting of E-cadherin using shRNA.For this purpose, after cell preparation EMT and CSCs markers in Pioglitazone and Cetuximab treated cells were assessed and compared with untreated cells using flow cytometry, real‐time PCR and microscopic monitoring. The findings showed mesenchymal morphology of HT29-shE changed to epithelial morphology after Pioglitazone and Cetuximab treatment, moreover E-cadherin expression increased and Vimentin expression decreased. In addition, expression of CSC markers (CD133+ and CD44+) were reduced in HT29-shE after treatment.