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Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells

Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in sta...

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Autores principales: Mo, Lihong, Pospichalova, Vendula, Huang, Zhiqing, Murphy, Susan K., Payne, Sturgis, Wang, Fang, Kennedy, Margaret, Cianciolo, George J., Bryja, Vitezslav, Pizzo, Salvatore V., Bachelder, Robin E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493087/
https://www.ncbi.nlm.nih.gov/pubmed/26148191
http://dx.doi.org/10.1371/journal.pone.0131579
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author Mo, Lihong
Pospichalova, Vendula
Huang, Zhiqing
Murphy, Susan K.
Payne, Sturgis
Wang, Fang
Kennedy, Margaret
Cianciolo, George J.
Bryja, Vitezslav
Pizzo, Salvatore V.
Bachelder, Robin E.
author_facet Mo, Lihong
Pospichalova, Vendula
Huang, Zhiqing
Murphy, Susan K.
Payne, Sturgis
Wang, Fang
Kennedy, Margaret
Cianciolo, George J.
Bryja, Vitezslav
Pizzo, Salvatore V.
Bachelder, Robin E.
author_sort Mo, Lihong
collection PubMed
description Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in stage III/IV ovarian cancer patients, ascites is associated with cancer progression. However, whether ascites drives multidrug resistance in ovarian cancer cells awaits elucidation. Here, we demonstrate that when cultured with ascites derived from ovarian cancer-bearing mice, a murine ovarian cancer cell line became less sensitive to paclitaxel, a first line chemotherapeutic agent for ovarian cancer patients. Moreover, incubation of murine ovarian cancer cells in vitro with ascites drives efflux function in these cells. Functional studies show ascites-driven efflux is suppressible by specific inhibitors of either of two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer Related Protein (BCRP)]. To demonstrate relevance of our findings to ovarian cancer patients, we studied relative efflux in human ovarian cancer cells obtained from either patient ascites or from primary tumor. Immortalized cell lines developed from human ascites show increased susceptibility to efflux inhibitors (MRP1, BCRP) compared to a cell line derived from a primary ovarian cancer, suggesting an association between ascites and efflux function in human ovarian cancer. Efflux in ascites-derived human ovarian cancer cells is associated with increased expression of ABC transporters compared to that in primary tumor-derived human ovarian cancer cells. Collectively, our findings identify a novel activity for ascites in promoting ovarian cancer multidrug resistance.
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spelling pubmed-44930872015-07-15 Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells Mo, Lihong Pospichalova, Vendula Huang, Zhiqing Murphy, Susan K. Payne, Sturgis Wang, Fang Kennedy, Margaret Cianciolo, George J. Bryja, Vitezslav Pizzo, Salvatore V. Bachelder, Robin E. PLoS One Research Article Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in stage III/IV ovarian cancer patients, ascites is associated with cancer progression. However, whether ascites drives multidrug resistance in ovarian cancer cells awaits elucidation. Here, we demonstrate that when cultured with ascites derived from ovarian cancer-bearing mice, a murine ovarian cancer cell line became less sensitive to paclitaxel, a first line chemotherapeutic agent for ovarian cancer patients. Moreover, incubation of murine ovarian cancer cells in vitro with ascites drives efflux function in these cells. Functional studies show ascites-driven efflux is suppressible by specific inhibitors of either of two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer Related Protein (BCRP)]. To demonstrate relevance of our findings to ovarian cancer patients, we studied relative efflux in human ovarian cancer cells obtained from either patient ascites or from primary tumor. Immortalized cell lines developed from human ascites show increased susceptibility to efflux inhibitors (MRP1, BCRP) compared to a cell line derived from a primary ovarian cancer, suggesting an association between ascites and efflux function in human ovarian cancer. Efflux in ascites-derived human ovarian cancer cells is associated with increased expression of ABC transporters compared to that in primary tumor-derived human ovarian cancer cells. Collectively, our findings identify a novel activity for ascites in promoting ovarian cancer multidrug resistance. Public Library of Science 2015-07-06 /pmc/articles/PMC4493087/ /pubmed/26148191 http://dx.doi.org/10.1371/journal.pone.0131579 Text en © 2015 Mo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mo, Lihong
Pospichalova, Vendula
Huang, Zhiqing
Murphy, Susan K.
Payne, Sturgis
Wang, Fang
Kennedy, Margaret
Cianciolo, George J.
Bryja, Vitezslav
Pizzo, Salvatore V.
Bachelder, Robin E.
Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
title Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
title_full Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
title_fullStr Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
title_full_unstemmed Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
title_short Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
title_sort ascites increases expression/function of multidrug resistance proteins in ovarian cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493087/
https://www.ncbi.nlm.nih.gov/pubmed/26148191
http://dx.doi.org/10.1371/journal.pone.0131579
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