Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma.
Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma.
复制标题
抑制 WEE1 可抑制喉鳞状细胞癌的肿瘤生长
DOI：
10.3389/fphar.2018.01041
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发表时间：
2018
影响因子：
5.6
通讯作者：
Shi Z
中科院分区：
文献类型：
--
作者：
Yuan ML;Li P;Xing ZH;Di JM;Liu H;Yang AK;Lin XJ;Jiang QW;Yang Y;Huang JR;Wang K;Wei MN;Li Y;Ye J;Shi Z
WEE 1是一种酪氨酸激酶，调节G2/M细胞周期检查点，并经常在各种肿瘤中过表达。然而，WEE 1在喉鳞状细胞癌（LSCC）中的表达及其临床意义尚不清楚。在本研究中，我们发现WEE 1在喉鳞状细胞癌组织中的表达高于癌旁正常组织。WEE 1的过表达与喉鳞癌的T分期、淋巴结转移、临床分期及预后密切相关。此外，MK-1775抑制WEE 1可诱导LSCC细胞生长抑制、细胞周期停滞和凋亡，并增加细胞内活性氧（ROS）水平。ROS清除剂N-乙酰-L-半胱氨酸预处理可逆转MK-1775诱导的LSCC细胞ROS积聚和细胞凋亡。MK-1775还抑制裸鼠中LSCC异种移植物的生长。总之，这些研究结果表明，WEE 1是一个潜在的治疗靶点在喉鳞状细胞癌，抑制WEE 1是喉鳞状细胞癌治疗的前瞻性策略。
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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影响因子：
3.9
作者：
Music, Darija;Dahlrot, Rikke Hedegaard;Kristensen, Bjarne Winther
通讯作者：
Kristensen, Bjarne Winther
影响因子：
4.7
作者：
Slipicevic, Ana;Holth, Arild;Florenes, Vivi Ann
通讯作者：
Florenes, Vivi Ann
影响因子：
5.7
作者：
Guertin, Amy D.;Li, Jing;Shumway, Stuart D.
通讯作者：
Shumway, Stuart D.
影响因子：
--
作者：
Egeland, Eivind Valen;Flatmark, Kjersti;Boye, Kjetil
通讯作者：
Boye, Kjetil
DOI：
10.1016/j.neo.2015.09.006
发表时间：
2015-10
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Kausar T;Schreiber JS;Karnak D;Parsels LA;Parsels JD;Davis MA;Zhao L;Maybaum J;Lawrence TS;Morgan MA
通讯作者：
Morgan MA