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Effect of Chemotherapeutic Agents on the Expression of Retinoid Receptors and Markers of Cancer Stem Cells and Epithelial-Mesenchymal Transition

O. Isayev1,4,a, Y. Zhu2,b, E. Gasimov1,c, J. Werner3, and A. V. Bazhin3,d*

1Department of Histology, Embryology and Cytology, Azerbaijan Medical University, AZ1022 Baku, Azerbaijan

2International Joint Laboratory for Cell Medical Engineering of Henan Province, Department of Oncology, Henan University Huaihe Hospital, Kaifeng, 475000 Henan, People’s Republic of China

3Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, 81377 Munich, Germany

4Genetic Resources Institute, Azerbaijan National Academy of Sciences, AZ1106 Baku, Azerbaijan

* To whom correspondence should be addressed.

Received May 14, 2019; Revised May 14, 2019; Accepted May 14, 2019
A large body of evidence suggests that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT), as well as expression and function of retinoid receptors, are pivotal features of tumor initiation, progression, and chemoresistance. This is also true for pancreatic ductal adenocarcinoma (PDAC), which represents a clinical challenge due to poor prognosis and increasing incidence. Understanding the above features of cancer cells could open new avenues for PDAC treatment strategies. The aim of this study was to investigate the relation between CSCs, EMT, and retinoid receptors in PDAC after treatment with the chemotherapeutic agents – gemcitabine and 5-fluorouracil. First, we demonstrated the difference in the expression levels of CSC and EMT markers and retinoid receptors in the untreated Mia PaCa-2 and Panc1 cells that also differed in the frequency of spontaneous apoptosis and distribution between the cell cycle phases. Chemotherapy reduced the number of cancer cells in the S phase. Gemcitabine and 5-fluorouracil modulated expression of CSC markers, E-cadherin, and RXRβ in Panc1 but not in Mia PaCa-2 cells. We suggest that these effects could be attributed to the difference in the basal levels of expression of the investigated genes. The obtained data could be interesting in the context of future preclinical research.
KEY WORDS: pancreatic ductal adenocarcinoma, cancer stem cells, epithelial-mesenchymal transition, retinoid receptors

DOI: 10.1134/S0006297919110166