Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors
Ezgi Kaşıkcı,1,2 Esra Aydemir,1 Ömer Faruk Bayrak,3 Fikrettin Şahin1 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 1...
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doaj-a070011dbb7f4ebe80da70fbf91c6aa92020-11-25T02:28:42ZengDove Medical PressOncoTargets and Therapy1178-69302020-06-01Volume 135763577754636Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule InhibitorsKaşıkcı EAydemir EBayrak ÖFŞahin FEzgi Kaşıkcı,1,2 Esra Aydemir,1 Ömer Faruk Bayrak,3 Fikrettin Şahin1 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, TurkeyCorrespondence: Ezgi Kaşıkcı Email ezgikasikci13@gmail.comPurpose: 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 drughttps://www.dovepress.com/inhibition-of-migration-invasion-and-drug-resistance-of-pancreatic-ade-peer-reviewed-article-OTTpancreatic cancermetastasiscanceremtgene therapyanti-cancer drug |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kaşıkcı E Aydemir E Bayrak ÖF Şahin F |
spellingShingle |
Kaşıkcı E Aydemir E Bayrak ÖF Şahin F Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors OncoTargets and Therapy pancreatic cancer metastasis cancer emt gene therapy anti-cancer drug |
author_facet |
Kaşıkcı E Aydemir E Bayrak ÖF Şahin F |
author_sort |
Kaşıkcı E |
title |
Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors |
title_short |
Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors |
title_full |
Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors |
title_fullStr |
Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors |
title_full_unstemmed |
Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells – Role of Snail, Slug and Twist and Small Molecule Inhibitors |
title_sort |
inhibition of migration, invasion and drug resistance of pancreatic adenocarcinoma cells – role of snail, slug and twist and small molecule inhibitors |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2020-06-01 |
description |
Ezgi Kaşıkcı,1,2 Esra Aydemir,1 Ömer Faruk Bayrak,3 Fikrettin Şahin1 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, TurkeyCorrespondence: Ezgi Kaşıkcı Email ezgikasikci13@gmail.comPurpose: 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 |
topic |
pancreatic cancer metastasis cancer emt gene therapy anti-cancer drug |
url |
https://www.dovepress.com/inhibition-of-migration-invasion-and-drug-resistance-of-pancreatic-ade-peer-reviewed-article-OTT |
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