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Effect of midkine on gemcitabine resistance in biliary tract cancer
Gemcitabine-based chemotherapy is one of the most effective and commonly used chemotherapeutic regimens for biliary tract cancer (BTC). However, development of resistance to this drug limits its efficacy. The present study aimed to explore the effects of midkine (MDK) on the resistance of BTC cells...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810218/ https://www.ncbi.nlm.nih.gov/pubmed/29344648 http://dx.doi.org/10.3892/ijmm.2018.3399 |
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author | Lu, Yongliang Yan, Bing Guo, Huihui Qiu, Li Sun, Xinrong Wang, Xiang Shi, Qian Bao, Ying |
author_facet | Lu, Yongliang Yan, Bing Guo, Huihui Qiu, Li Sun, Xinrong Wang, Xiang Shi, Qian Bao, Ying |
author_sort | Lu, Yongliang |
collection | PubMed |
description | Gemcitabine-based chemotherapy is one of the most effective and commonly used chemotherapeutic regimens for biliary tract cancer (BTC). However, development of resistance to this drug limits its efficacy. The present study aimed to explore the effects of midkine (MDK) on the resistance of BTC cells to gemcitabine. Cell viability and proliferation were measured by a Cell Counting Kit-8 assay and 5-ethynyl-2′-deoxyuridine staining, respectively. Western blot analysis was used to detect the expression of E-cadherin and vimentin. The results indicated that BTC cell lines were more resistant to gemcitabine plus MDK compared with gemcitabine alone. In terms of the underlying mechanism, MDK promoted the epithelial to mesenchymal transition (EMT) of BTC cells and the enhancing effect of MDK on gemcitabine resistance was abrogated when the EMT was blocked with small interfering (si)RNA targeting Twist. In addition, MDK promoted the expression of Notch-1, while knockdown of Notch-1 by siRNA blocked the EMT process in the BTC cell lines. Taken together, these results indicated that MDK promoted gemcitabine resistance of BTC through inducing EMT via upregulating Notch-1. It was suggested that inhibition of the EMT is a promising strategy to overcome MDK-induced drug resistance. |
format | Online Article Text |
id | pubmed-5810218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-58102182018-02-27 Effect of midkine on gemcitabine resistance in biliary tract cancer Lu, Yongliang Yan, Bing Guo, Huihui Qiu, Li Sun, Xinrong Wang, Xiang Shi, Qian Bao, Ying Int J Mol Med Articles Gemcitabine-based chemotherapy is one of the most effective and commonly used chemotherapeutic regimens for biliary tract cancer (BTC). However, development of resistance to this drug limits its efficacy. The present study aimed to explore the effects of midkine (MDK) on the resistance of BTC cells to gemcitabine. Cell viability and proliferation were measured by a Cell Counting Kit-8 assay and 5-ethynyl-2′-deoxyuridine staining, respectively. Western blot analysis was used to detect the expression of E-cadherin and vimentin. The results indicated that BTC cell lines were more resistant to gemcitabine plus MDK compared with gemcitabine alone. In terms of the underlying mechanism, MDK promoted the epithelial to mesenchymal transition (EMT) of BTC cells and the enhancing effect of MDK on gemcitabine resistance was abrogated when the EMT was blocked with small interfering (si)RNA targeting Twist. In addition, MDK promoted the expression of Notch-1, while knockdown of Notch-1 by siRNA blocked the EMT process in the BTC cell lines. Taken together, these results indicated that MDK promoted gemcitabine resistance of BTC through inducing EMT via upregulating Notch-1. It was suggested that inhibition of the EMT is a promising strategy to overcome MDK-induced drug resistance. D.A. Spandidos 2018-04 2018-01-18 /pmc/articles/PMC5810218/ /pubmed/29344648 http://dx.doi.org/10.3892/ijmm.2018.3399 Text en Copyright: © Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Lu, Yongliang Yan, Bing Guo, Huihui Qiu, Li Sun, Xinrong Wang, Xiang Shi, Qian Bao, Ying Effect of midkine on gemcitabine resistance in biliary tract cancer |
title | Effect of midkine on gemcitabine resistance in biliary tract cancer |
title_full | Effect of midkine on gemcitabine resistance in biliary tract cancer |
title_fullStr | Effect of midkine on gemcitabine resistance in biliary tract cancer |
title_full_unstemmed | Effect of midkine on gemcitabine resistance in biliary tract cancer |
title_short | Effect of midkine on gemcitabine resistance in biliary tract cancer |
title_sort | effect of midkine on gemcitabine resistance in biliary tract cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810218/ https://www.ncbi.nlm.nih.gov/pubmed/29344648 http://dx.doi.org/10.3892/ijmm.2018.3399 |
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