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@article{1316066,
author = {Lihong, M.o. and Pospíchalová, Vendula and Huang, Z.Q. and Murphy, S.K. and Payne, S. and Wang, Fan and Kennedy, M. and Cianciolo, G.J. and Bryja, Vítězslav and Pizzo, S.V. and Bachelder, R.E.},
article_location = {San Francisco},
article_number = {7},
doi = {http://dx.doi.org/10.1371/journal.pone.0131579},
keywords = {CHEMOTHERAPY; SURVIVAL; GENE; TRANSPORTERS; KINASE; MDR1},
language = {eng},
issn = {1932-6203},
journal = {Plos one},
title = {Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells},
url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131579},
volume = {10},
year = {2015}
}
TY - JOUR
ID - 1316066
AU - Lihong, M.o. - Pospíchalová, Vendula - Huang, Z.Q. - Murphy, S.K. - Payne, S. - Wang, Fan - Kennedy, M. - Cianciolo, G.J. - Bryja, Vítězslav - Pizzo, S.V. - Bachelder, R.E.
PY - 2015
TI - Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells
JF - Plos one
VL - 10
IS - 7
SP - "nestránkováno"
EP - "nestránkováno"
PB - Public Library of Science
SN - 19326203
KW - CHEMOTHERAPY
KW - SURVIVAL
KW - GENE
KW - TRANSPORTERS
KW - KINASE
KW - MDR1
UR - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131579
L2 - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131579
N2 - 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.
ER -
LIHONG, M.o., Vendula POSPÍCHALOVÁ, Z.Q. HUANG, S.K. MURPHY, S. PAYNE, Fan WANG, M. KENNEDY, G.J. CIANCIOLO, Vítězslav BRYJA, S.V. PIZZO and R.E. BACHELDER. Ascites Increases Expression/Function of Multidrug Resistance Proteins in Ovarian Cancer Cells. \textit{Plos one}. San Francisco: Public Library of Science, 2015, vol.~10, No~7, p.~''nestránkováno'', 15 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0131579.
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