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Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype
The major cause of failure in cancer chemotherapy is the development of multidrug resistance (MDR), and the characterization of biological factors involved in this response to therapy is particularly needed. A doxorubicin‐resistant HCT‐8/R clone was selected from sensitive parental cells and charact...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924386/ https://www.ncbi.nlm.nih.gov/pubmed/27016279 http://dx.doi.org/10.1002/cam4.694 |
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author | Cinci, Lorenzo Luceri, Cristina Bigagli, Elisabetta Carboni, Ilaria Paccosi, Sara Parenti, Astrid Guasti, Daniele Coronnello, Marcella |
author_facet | Cinci, Lorenzo Luceri, Cristina Bigagli, Elisabetta Carboni, Ilaria Paccosi, Sara Parenti, Astrid Guasti, Daniele Coronnello, Marcella |
author_sort | Cinci, Lorenzo |
collection | PubMed |
description | The major cause of failure in cancer chemotherapy is the development of multidrug resistance (MDR), and the characterization of biological factors involved in this response to therapy is particularly needed. A doxorubicin‐resistant HCT‐8/R clone was selected from sensitive parental cells and characterized analyzing several parameters (cell cycle phase distribution, apoptotic activity, expression, distribution and functionality of the P‐gp efflux pump, the response to other chemotherapy agents, its ultrastructural features, invasiveness, and transcriptomic profile). HCT‐8/R cells showed a peculiar S phase distribution, characterized by a single pulse of proliferation, resistance to drug‐mediated apoptosis, increased expression and functionality of P‐gp and overexpression of stem cell markers (CD44 and aldehyde dehydrogenase 1A2). At the ultrastructural level, HCT‐8/R presented a greater cell volume and several intracytoplasmic vesicles respect to HCT‐8. Moreover, the resistant clone was characterized by cross resistance to other cytotoxic drugs and a greater capacity for migration and invasion, compared to parental cells. Our data reinforce the concept that the MDR phenotype in HCT‐8/R cells is multifactorial and involves multiple mechanisms, representing an interesting tool to understand the biological basis of MDR and to test strategies that overcome resistance to chemotherapy. |
format | Online Article Text |
id | pubmed-4924386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49243862016-06-29 Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype Cinci, Lorenzo Luceri, Cristina Bigagli, Elisabetta Carboni, Ilaria Paccosi, Sara Parenti, Astrid Guasti, Daniele Coronnello, Marcella Cancer Med Cancer Biology The major cause of failure in cancer chemotherapy is the development of multidrug resistance (MDR), and the characterization of biological factors involved in this response to therapy is particularly needed. A doxorubicin‐resistant HCT‐8/R clone was selected from sensitive parental cells and characterized analyzing several parameters (cell cycle phase distribution, apoptotic activity, expression, distribution and functionality of the P‐gp efflux pump, the response to other chemotherapy agents, its ultrastructural features, invasiveness, and transcriptomic profile). HCT‐8/R cells showed a peculiar S phase distribution, characterized by a single pulse of proliferation, resistance to drug‐mediated apoptosis, increased expression and functionality of P‐gp and overexpression of stem cell markers (CD44 and aldehyde dehydrogenase 1A2). At the ultrastructural level, HCT‐8/R presented a greater cell volume and several intracytoplasmic vesicles respect to HCT‐8. Moreover, the resistant clone was characterized by cross resistance to other cytotoxic drugs and a greater capacity for migration and invasion, compared to parental cells. Our data reinforce the concept that the MDR phenotype in HCT‐8/R cells is multifactorial and involves multiple mechanisms, representing an interesting tool to understand the biological basis of MDR and to test strategies that overcome resistance to chemotherapy. John Wiley and Sons Inc. 2016-03-25 /pmc/articles/PMC4924386/ /pubmed/27016279 http://dx.doi.org/10.1002/cam4.694 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Cinci, Lorenzo Luceri, Cristina Bigagli, Elisabetta Carboni, Ilaria Paccosi, Sara Parenti, Astrid Guasti, Daniele Coronnello, Marcella Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype |
title | Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype |
title_full | Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype |
title_fullStr | Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype |
title_full_unstemmed | Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype |
title_short | Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype |
title_sort | development and characterization of an in vitro model of colorectal adenocarcinoma with mdr phenotype |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924386/ https://www.ncbi.nlm.nih.gov/pubmed/27016279 http://dx.doi.org/10.1002/cam4.694 |
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