Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000607 |
Resumo: | Chemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma. |
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Brazilian Journal of Medical and Biological Research |
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Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5ChemotherapyCholangiocarcinomaDrug resistanceDoxorubicinSalinomycinChemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma.Associação Brasileira de Divulgação Científica2017-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000607Brazilian Journal of Medical and Biological Research v.50 n.10 2017reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/1414-431x20176147info:eu-repo/semantics/openAccessYu,Z.Cheng,H.Zhu,H.Cao,M.Lu,C.Bao,S.Pan,Y.Li,Y.eng2019-03-19T00:00:00Zoai:scielo:S0100-879X2017001000607Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2019-03-19T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
title |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
spellingShingle |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 Yu,Z. Chemotherapy Cholangiocarcinoma Drug resistance Doxorubicin Salinomycin |
title_short |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
title_full |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
title_fullStr |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
title_full_unstemmed |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
title_sort |
Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5 |
author |
Yu,Z. |
author_facet |
Yu,Z. Cheng,H. Zhu,H. Cao,M. Lu,C. Bao,S. Pan,Y. Li,Y. |
author_role |
author |
author2 |
Cheng,H. Zhu,H. Cao,M. Lu,C. Bao,S. Pan,Y. Li,Y. |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Yu,Z. Cheng,H. Zhu,H. Cao,M. Lu,C. Bao,S. Pan,Y. Li,Y. |
dc.subject.por.fl_str_mv |
Chemotherapy Cholangiocarcinoma Drug resistance Doxorubicin Salinomycin |
topic |
Chemotherapy Cholangiocarcinoma Drug resistance Doxorubicin Salinomycin |
description |
Chemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000607 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000607 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1414-431x20176147 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.50 n.10 2017 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
_version_ |
1754302945868906496 |