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Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells

Liver kinase B1 (LKB1) is a well-known tumor suppressor gene in a variety of human cancers, including breast cancer. However, its role in gemcitabine resistance is unclear. Since gemcitabine in combination with other chemotherapeutic reagents is the first-line treatment in advanced breast cancer, th...

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Autores principales: XIA, CHEN, YE, FUGUI, HU, XIN, LI, ZHENGDONG, JIANG, BEIQI, FU, YUN, CHENG, XIAOLIN, SHAO, ZHIMING, ZHUANG, ZHIGANG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186618/
https://www.ncbi.nlm.nih.gov/pubmed/25295095
http://dx.doi.org/10.3892/ol.2014.2446
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author XIA, CHEN
YE, FUGUI
HU, XIN
LI, ZHENGDONG
JIANG, BEIQI
FU, YUN
CHENG, XIAOLIN
SHAO, ZHIMING
ZHUANG, ZHIGANG
author_facet XIA, CHEN
YE, FUGUI
HU, XIN
LI, ZHENGDONG
JIANG, BEIQI
FU, YUN
CHENG, XIAOLIN
SHAO, ZHIMING
ZHUANG, ZHIGANG
author_sort XIA, CHEN
collection PubMed
description Liver kinase B1 (LKB1) is a well-known tumor suppressor gene in a variety of human cancers, including breast cancer. However, its role in gemcitabine resistance is unclear. Since gemcitabine in combination with other chemotherapeutic reagents is the first-line treatment in advanced breast cancer, the aim of the present study was to determine the effect of ectopic expression of LKB1 on chemosensitivity to gemcitabine in the breast cancer MDA-MB-231 cell line. Increasing the expression of LKB1 was found to directly correlate with gemcitabine chemoresistance. Although LKB1 suppressed the cell proliferation rate and clonogenicity in the absence of gemcitabine, it increased the median inhibitory concentration of gemcitabine and clonogenicity of cells in the presence of gemcitabine. Mechanistic analysis indicated that LKB1 was able to protect cells from DNA damage caused by gemcitabine. Furthermore, it was found that LKB1 induced a significant upregulation of cytidine deaminase expression, an important enzyme that accelerates gemcitabine catabolization. Overall, dual characteristics of LKB1 were identified: Suppressing cell growth in normal conditions and enhancing chemoresisitance to gemcitabine, possibly by accelerating degradation of gemcitabine, and protecting cells from DNA damage caused by gemcitabine.
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spelling pubmed-41866182014-10-07 Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells XIA, CHEN YE, FUGUI HU, XIN LI, ZHENGDONG JIANG, BEIQI FU, YUN CHENG, XIAOLIN SHAO, ZHIMING ZHUANG, ZHIGANG Oncol Lett Articles Liver kinase B1 (LKB1) is a well-known tumor suppressor gene in a variety of human cancers, including breast cancer. However, its role in gemcitabine resistance is unclear. Since gemcitabine in combination with other chemotherapeutic reagents is the first-line treatment in advanced breast cancer, the aim of the present study was to determine the effect of ectopic expression of LKB1 on chemosensitivity to gemcitabine in the breast cancer MDA-MB-231 cell line. Increasing the expression of LKB1 was found to directly correlate with gemcitabine chemoresistance. Although LKB1 suppressed the cell proliferation rate and clonogenicity in the absence of gemcitabine, it increased the median inhibitory concentration of gemcitabine and clonogenicity of cells in the presence of gemcitabine. Mechanistic analysis indicated that LKB1 was able to protect cells from DNA damage caused by gemcitabine. Furthermore, it was found that LKB1 induced a significant upregulation of cytidine deaminase expression, an important enzyme that accelerates gemcitabine catabolization. Overall, dual characteristics of LKB1 were identified: Suppressing cell growth in normal conditions and enhancing chemoresisitance to gemcitabine, possibly by accelerating degradation of gemcitabine, and protecting cells from DNA damage caused by gemcitabine. D.A. Spandidos 2014-11 2014-08-14 /pmc/articles/PMC4186618/ /pubmed/25295095 http://dx.doi.org/10.3892/ol.2014.2446 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
XIA, CHEN
YE, FUGUI
HU, XIN
LI, ZHENGDONG
JIANG, BEIQI
FU, YUN
CHENG, XIAOLIN
SHAO, ZHIMING
ZHUANG, ZHIGANG
Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells
title Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells
title_full Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells
title_fullStr Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells
title_full_unstemmed Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells
title_short Liver kinase B1 enhances chemoresistance to gemcitabine in breast cancer MDA-MB-231 cells
title_sort liver kinase b1 enhances chemoresistance to gemcitabine in breast cancer mda-mb-231 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186618/
https://www.ncbi.nlm.nih.gov/pubmed/25295095
http://dx.doi.org/10.3892/ol.2014.2446
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