4.7 Article

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

Journal

FRONTIERS IN PHARMACOLOGY
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2018.01041

Keywords

laryngeal squamous cell carcinoma; WEE1; MK-1775; cell cycle; apoptosis; reactive oxygen species

Funding

  1. National Key Research and Development Program of China [2017YFA0505104]
  2. National Natural Science Foundation of China [81772540, 81772752]
  3. Guangdong Natural Science Funds for Distinguished Young Scholar [2014A030306001]
  4. Guangdong Special Support Program for Young Talent [2015TQ01R350]
  5. Science and Technology Program of Guangdong [2016A050502027, 2017A020215122]
  6. Science and Technology Program of Guangzhou [201704030058, 201709010038]

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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.

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