Abstract
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.
Highlights
Laryngeal carcinoma is the second most common malignant tumor of the respiratory system in the male compared to its relative rare in the female (Siegel et al, 2018)
To further explore whether WEE1 is a therapeutic target in laryngeal squamous cell carcinoma (LSCC), we examined the protein expression of WEE1 and cytotoxicity of a WEE1 inhibitor MK-1775 in LSCC cells
reactive oxygen species (ROS) goes up when cells prematurely enter mitosis, and that the increased ROS drives cell death (Marchetti et al, 2006). To confirm that this was occurring we detected the intracellular level of ROS in MK-1775-treated LSCC cells, we found ROS significantly increased following Wee1 inhibition, and we could limit death by reducing ROS with NAC
Summary
Laryngeal carcinoma is the second most common malignant tumor of the respiratory system in the male compared to its relative rare in the female (Siegel et al, 2018). Prior work has demonstrated that ectopic high-expression of WEE1 has been identified in Inhibition of WEE1 Suppresses the Growth of LSCC several malignant tumors and associated with poor outcome, such as glioblastoma (Music et al, 2016), vulvar squamous cell carcinoma (Magnussen et al, 2013), ovarian carcinoma (Slipicevic et al, 2014), melanoma (Magnussen et al, 2012), and colorectal carcinoma (Egeland et al, 2016; Ge et al, 2017). The expression and clinical significance of WEE1 in LSCC are still unknown. We have investigated the expression and clinical significance of WEE1 in LSCC, and the anti-tumor effects and mechanisms of WEE1 inhibition against LSCC
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