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Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma

WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in...

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Autores principales: Yuan, Meng-Ling, Li, Pei, Xing, Zi-Hao, Di, Jin-Ming, Liu, Hui, Yang, An-Kui, Lin, Xi-Jun, Jiang, Qi-Wei, Yang, Yang, Huang, Jia-Rong, Wang, Kun, Wei, Meng-Ning, Li, Yao, Ye, Jin, Shi, Zhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172786/
https://www.ncbi.nlm.nih.gov/pubmed/30323762
http://dx.doi.org/10.3389/fphar.2018.01041
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author Yuan, Meng-Ling
Li, Pei
Xing, Zi-Hao
Di, Jin-Ming
Liu, Hui
Yang, An-Kui
Lin, Xi-Jun
Jiang, Qi-Wei
Yang, Yang
Huang, Jia-Rong
Wang, Kun
Wei, Meng-Ning
Li, Yao
Ye, Jin
Shi, Zhi
author_facet Yuan, Meng-Ling
Li, Pei
Xing, Zi-Hao
Di, Jin-Ming
Liu, Hui
Yang, An-Kui
Lin, Xi-Jun
Jiang, Qi-Wei
Yang, Yang
Huang, Jia-Rong
Wang, Kun
Wei, Meng-Ning
Li, Yao
Ye, Jin
Shi, Zhi
author_sort Yuan, Meng-Ling
collection PubMed
description WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in LSCC tissues compared with adjacent normal tissues. Importantly, overexpression of WEE1 was correlated with T stages, lymph node metastasis, clinical stages and poor prognosis of LSCC patients. Furthermore, inhibition of WEE1 by MK-1775 induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular reactive oxygen species (ROS) levels in LSCC cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse MK-1775-induced ROS accumulation and cell apoptosis in LSCC cells. MK-1775 also inhibited the growth of LSCC xenografts in nude mice. Altogether, these findings suggest that WEE1 is a potential therapeutic target in LSCC, and inhibition of WEE1 is the prospective strategy for LSCC therapy.
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spelling pubmed-61727862018-10-15 Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma Yuan, Meng-Ling Li, Pei Xing, Zi-Hao Di, Jin-Ming Liu, Hui Yang, An-Kui Lin, Xi-Jun Jiang, Qi-Wei Yang, Yang Huang, Jia-Rong Wang, Kun Wei, Meng-Ning Li, Yao Ye, Jin Shi, Zhi Front Pharmacol Pharmacology WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in LSCC tissues compared with adjacent normal tissues. Importantly, overexpression of WEE1 was correlated with T stages, lymph node metastasis, clinical stages and poor prognosis of LSCC patients. Furthermore, inhibition of WEE1 by MK-1775 induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular reactive oxygen species (ROS) levels in LSCC cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse MK-1775-induced ROS accumulation and cell apoptosis in LSCC cells. MK-1775 also inhibited the growth of LSCC xenografts in nude mice. Altogether, these findings suggest that WEE1 is a potential therapeutic target in LSCC, and inhibition of WEE1 is the prospective strategy for LSCC therapy. Frontiers Media S.A. 2018-09-28 /pmc/articles/PMC6172786/ /pubmed/30323762 http://dx.doi.org/10.3389/fphar.2018.01041 Text en Copyright © 2018 Yuan, Li, Xing, Di, Liu, Yang, Lin, Jiang, Yang, Huang, Wang, Wei, Li, Ye and Shi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yuan, Meng-Ling
Li, Pei
Xing, Zi-Hao
Di, Jin-Ming
Liu, Hui
Yang, An-Kui
Lin, Xi-Jun
Jiang, Qi-Wei
Yang, Yang
Huang, Jia-Rong
Wang, Kun
Wei, Meng-Ning
Li, Yao
Ye, Jin
Shi, Zhi
Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
title Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
title_full Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
title_fullStr Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
title_full_unstemmed Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
title_short Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma
title_sort inhibition of wee1 suppresses the tumor growth in laryngeal squamous cell carcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172786/
https://www.ncbi.nlm.nih.gov/pubmed/30323762
http://dx.doi.org/10.3389/fphar.2018.01041
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