PMID- 30323762 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220410 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 9 DP - 2018 TI - Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma. PG - 1041 LID - 10.3389/fphar.2018.01041 [doi] LID - 1041 AB - 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. FAU - Yuan, Meng-Ling AU - Yuan ML AD - 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. FAU - Li, Pei AU - Li P AD - Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Xing, Zi-Hao AU - Xing ZH AD - 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. FAU - Di, Jin-Ming AU - Di JM AD - Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Liu, Hui AU - Liu H AD - Division of Pulmonary and Critical Care, Department of Internal Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Yang, An-Kui AU - Yang AK AD - 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. FAU - Lin, Xi-Jun AU - Lin XJ AD - Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Jiang, Qi-Wei AU - Jiang QW AD - 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. FAU - Yang, Yang AU - Yang Y AD - 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. FAU - Huang, Jia-Rong AU - Huang JR AD - 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. FAU - Wang, Kun AU - Wang K AD - 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. FAU - Wei, Meng-Ning AU - Wei MN AD - 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. FAU - Li, Yao AU - Li Y AD - 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. FAU - Ye, Jin AU - Ye J AD - Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Shi, Zhi AU - Shi Z AD - 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. LA - eng PT - Journal Article DEP - 20180928 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC6172786 OTO - NOTNLM OT - MK-1775 OT - WEE1 OT - apoptosis OT - cell cycle OT - laryngeal squamous cell carcinoma OT - reactive oxygen species EDAT- 2018/10/17 06:00 MHDA- 2018/10/17 06:01 PMCR- 2018/09/28 CRDT- 2018/10/17 06:00 PHST- 2018/06/12 00:00 [received] PHST- 2018/08/27 00:00 [accepted] PHST- 2018/10/17 06:00 [entrez] PHST- 2018/10/17 06:00 [pubmed] PHST- 2018/10/17 06:01 [medline] PHST- 2018/09/28 00:00 [pmc-release] AID - 10.3389/fphar.2018.01041 [doi] PST - epublish SO - Front Pharmacol. 2018 Sep 28;9:1041. doi: 10.3389/fphar.2018.01041. eCollection 2018.