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The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors
BACKGROUND/AIM: Currently, it has been proposed that combination of 5-fluorouracil (5FU) with inhibitors of the mitogen-activated protein kinases (MAPKs) signaling pathway might enhance the efficacy of 5FU-based chemotherapy in colon cancer. Our study aimed to investigate an impact of TWIST1 silenci...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848323/ https://www.ncbi.nlm.nih.gov/pubmed/29451183 http://dx.doi.org/10.4103/sjg.SJG_270_17 |
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author | Przybyla, Tomasz Wesserling, Martyna Sakowicz-Burkiewicz, Monika Maciejewska, Izabela Pawelczyk, Tadeusz |
author_facet | Przybyla, Tomasz Wesserling, Martyna Sakowicz-Burkiewicz, Monika Maciejewska, Izabela Pawelczyk, Tadeusz |
author_sort | Przybyla, Tomasz |
collection | PubMed |
description | BACKGROUND/AIM: Currently, it has been proposed that combination of 5-fluorouracil (5FU) with inhibitors of the mitogen-activated protein kinases (MAPKs) signaling pathway might enhance the efficacy of 5FU-based chemotherapy in colon cancer. Our study aimed to investigate an impact of TWIST1 silencing on the sensitivity of cancer cells to 5FU and selected MAPK inhibitors. MATERIALS AND METHODS: The suppression of TWIST1 expression in human colon cancer HT29 and HCT116 cell lines was achieved by transduction with lentiviral vector carrying the TWIST1 silencing sequence (pLL3.7-sh TWIST1). The statistical calculation was performed with analysis of variance or Dunnett's test for comparison to control group. Paired Student's t-test was performed when two groups were analyzed. RESULTS: Suppression of TWIST1 reduced the proliferation rate of colon cancer cells and enhanced their sensitivity to 5FU and MAPKs inhibitors. The sensitivity of HT29 cells to examined compounds was more dependent on TWIST1 expression level compared to HCT116 cells. The most noticeable effect of TWIST1 suppression on sensitivity of both colon cancer cell lines to combined treatment of 5FU and the MAPKs inhibitors was observed for inhibitors of p38α/β and JNK1-3. We also noted that the suppression of TWIST1 significantly sensitized both cell lines to combined treatment of 5FU and Rac inhibitor. CONCLUSIONS: Our observations point to TWIST1 expression level as a marker of colon cancer sensitivity to combined treatment of 5FU and MAPKs inhibitors. |
format | Online Article Text |
id | pubmed-5848323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-58483232018-03-21 The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors Przybyla, Tomasz Wesserling, Martyna Sakowicz-Burkiewicz, Monika Maciejewska, Izabela Pawelczyk, Tadeusz Saudi J Gastroenterol Original Article BACKGROUND/AIM: Currently, it has been proposed that combination of 5-fluorouracil (5FU) with inhibitors of the mitogen-activated protein kinases (MAPKs) signaling pathway might enhance the efficacy of 5FU-based chemotherapy in colon cancer. Our study aimed to investigate an impact of TWIST1 silencing on the sensitivity of cancer cells to 5FU and selected MAPK inhibitors. MATERIALS AND METHODS: The suppression of TWIST1 expression in human colon cancer HT29 and HCT116 cell lines was achieved by transduction with lentiviral vector carrying the TWIST1 silencing sequence (pLL3.7-sh TWIST1). The statistical calculation was performed with analysis of variance or Dunnett's test for comparison to control group. Paired Student's t-test was performed when two groups were analyzed. RESULTS: Suppression of TWIST1 reduced the proliferation rate of colon cancer cells and enhanced their sensitivity to 5FU and MAPKs inhibitors. The sensitivity of HT29 cells to examined compounds was more dependent on TWIST1 expression level compared to HCT116 cells. The most noticeable effect of TWIST1 suppression on sensitivity of both colon cancer cell lines to combined treatment of 5FU and the MAPKs inhibitors was observed for inhibitors of p38α/β and JNK1-3. We also noted that the suppression of TWIST1 significantly sensitized both cell lines to combined treatment of 5FU and Rac inhibitor. CONCLUSIONS: Our observations point to TWIST1 expression level as a marker of colon cancer sensitivity to combined treatment of 5FU and MAPKs inhibitors. Medknow Publications & Media Pvt Ltd 2018 /pmc/articles/PMC5848323/ /pubmed/29451183 http://dx.doi.org/10.4103/sjg.SJG_270_17 Text en Copyright: © 2018 Saudi Journal of Gastroenterology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Przybyla, Tomasz Wesserling, Martyna Sakowicz-Burkiewicz, Monika Maciejewska, Izabela Pawelczyk, Tadeusz The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
title | The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
title_full | The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
title_fullStr | The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
title_full_unstemmed | The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
title_short | The Level of TWIST1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
title_sort | level of twist1 expression determines the response of colon cancer cells to mitogen-activated protein kinases inhibitors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848323/ https://www.ncbi.nlm.nih.gov/pubmed/29451183 http://dx.doi.org/10.4103/sjg.SJG_270_17 |
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