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

Meng-Ling Yuan; Pei Li; Zi-Hao Xing; Jin-Ming Di; Hui Liu; An-Kui Yang; Xi-Jun Lin; Qi-Wei Jiang; Yang Yang; Jia-Rong Huang; Kun Wang; Meng-Ning Wei; Yao Li; Jin Ye; Zhi Shi

doi:10.3389/fphar.2018.01041

Frontiers in Pharmacology (Sep 2018)

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

Meng-Ling Yuan,
Pei Li,
Zi-Hao Xing,
Jin-Ming Di,
Hui Liu,
An-Kui Yang,
Xi-Jun Lin,
Qi-Wei Jiang,
Yang Yang,
Jia-Rong Huang,
Kun Wang,
Meng-Ning Wei,
Yao Li,
Jin Ye,
Zhi Shi

Affiliations

Meng-Ling Yuan: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Pei Li: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Zi-Hao Xing: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Jin-Ming Di: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Hui Liu: Division of Pulmonary and Critical Care, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
An-Kui Yang: Department of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Xi-Jun Lin: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Qi-Wei Jiang: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Yang Yang: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Jia-Rong Huang: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Kun Wang: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Meng-Ning Wei: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Yao Li: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China
Jin Ye: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Zhi Shi: Department of Cell Biology – Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China

DOI: https://doi.org/10.3389/fphar.2018.01041
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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