Ezgi Kakc,1,2 Esra Aydemir,1 mer Faruk Bayrak,3 Fikrettin ahin1

1Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul 34755, Turkey; 2Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; 3Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul 34718, Turkey

Correspondence: Ezgi Kakc Email ezgikasikci13@gmail.com

Purpose: The main purpose of this study is to demonstrate the effects of epithelial to mesenchymal transition activating transcription factor silencing (EMT-ATF silencing) on migration, invasion, drug resistance and tumor-forming abilities of various pancreatic cancer cell lines. Additionally, the contribution of small molecule inhibitors of EMT (SD-208 and CX4945) to the effects of gene silencing was evaluated. Methods: EMT activating transcription factors Snail, Slug and Twist were silenced by short hairpins on Panc-1, MIA PaCa-2, BxPC-3, and AsPC-1 pancreatic cancer cell lines. The changes in migration, invasion, laminin attachment, cancer stem-like cell properties and tumor-forming abilities were investigated. Chemosensitivity assays and small molecule inhibitors of EMT were applied to the metastatic pancreatic cancer cell line AsPC-1. Results: EMT-ATF silencing reduced EMT and stem cell-like characteristics of pancreatic cancer cell lines. Following EMT-ATF silencing amongst the four PC cell lines, AsPC-1 showed the best response and was chosen for further chemoresistance and combinational therapy applications. EMT downregulated AsPC-1 cells showed less resistance to select chemotherapeutics compared to the control group. Both small molecule inhibitors enhanced the outcomes of EMT-ATF silencing. Conclusion: Overall it was found that EMT-ATF silencing, either by EMT-ATF silencing or with the enhancement by small molecules, is a good candidate to treat pancreatic cancer since it simultaneously minimizes metastasis, stem cell properties, and drug resistance.

Keywords: pancreatic cancer, metastasis, cancer, EMT, gene therapy, anti-cancer drug

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Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Ad | OTT - Dove Medical Press