Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Yongliang, Yan, Bing, Guo, Huihui, Qiu, Li, Sun, Xinrong, Wang, Xiang, Shi, Qian, Bao, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
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
_version_ 1783299710936678400
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
work_keys_str_mv AT luyongliang effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT yanbing effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT guohuihui effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT qiuli effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT sunxinrong effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT wangxiang effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT shiqian effectofmidkineongemcitabineresistanceinbiliarytractcancer
AT baoying effectofmidkineongemcitabineresistanceinbiliarytractcancer