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

J 2015

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

LIHONG, M.o., Vendula POSPÍCHALOVÁ, Z.Q. HUANG, S.K. MURPHY, S. PAYNE et. al.

Basic information

Original name

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

Authors

LIHONG, M.o. (840 United States of America), Vendula POSPÍCHALOVÁ (840 United States of America, belonging to the institution), Z.Q. HUANG (840 United States of America), S.K. MURPHY (840 United States of America), S. PAYNE (840 United States of America), Fan WANG (840 United States of America, belonging to the institution), M. KENNEDY (840 United States of America), G.J. CIANCIOLO (840 United States of America), Vítězslav BRYJA (203 Czech Republic, belonging to the institution), S.V. PIZZO (840 United States of America) and R.E. BACHELDER (840 United States of America)

Edition

Plos one, San Francisco, Public Library of Science, 2015, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.057

RIV identification code

RIV/00216224:14310/15:00084540

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1371/journal.pone.0131579

UT WoS

000358157600111

Keywords in English

CHEMOTHERAPY; SURVIVAL; GENE; TRANSPORTERS; KINASE; MDR1

Abstract

V originále

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.

Links

EE2.3.30.0009, research and development project

Name: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

Citovat

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. 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.

@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.

Detailed Information on Publication Record