XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway.
XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway.
复制标题
XAV939通过WNT通路抑制肺腺癌A549细胞的增殖和迁移
DOI：
10.3892/ol.2018.8491
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发表时间：
2018-06
期刊：
影响因子：
2.9
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Li C;Zheng X;Han Y;Lv Y;Lan F;Zhao J
本研究旨在探讨端锚聚合酶（tankyrase，TNKS）小分子抑制剂XAV 939对肺腺癌A549细胞增殖和迁移的影响及其可能机制。为此，研究了TNKS与肺腺泡腺癌中WNT/β-连环蛋白信号通路之间的关联。免疫组化结果显示，TNKS、β-catenin和Myc蛋白在肺腺癌组织中呈阳性表达，其表达水平明显高于癌旁正常组织。在所有检查的XAV 939干预组中，A549细胞增殖被抑制。在伤口愈合测定中，与对照组相比，用不同浓度的XAV 939处理的细胞表现出显著增加的划痕宽度。逆转录-半定量聚合酶链反应分析显示，与对照组相比，不同浓度的XAV 939可显著降低A549细胞中β-catenin mRNA的表达。免疫荧光显示，β-连环蛋白最初定位于细胞核/细胞质中，逐渐移位至细胞质/细胞膜，这是一种与药物浓度增加相关的效应。与未处理的细胞相比，用XAV 939处理的A549细胞中TNKS、β-catenin和c-Myc蛋白表达降低。因此，TNKS异常高表达可能促进肺癌的发生。TNKS抑制剂XAV 939在体外抑制肺腺癌A549细胞的增殖和迁移。XAV 939发挥其抑制作用的潜在机制可能与WNT信号通路的衰减有关。
The present study assessed the effects of the tankyrase (TNKS) small molecule inhibitor XAV939 on the proliferation and migration of lung adenocarcinoma A549 cells and the possible underlying mechanism. To do this, the association between TNKS and the WNT/β-catenin signaling pathway in lung acinar adenocarcinoma was investigated. Immunohistochemistry was performed, which demonstrated that TNKS, β-catenin and Myc proto-oncogene protein (c-Myc) proteins are positively expressed in lung adenocarcinoma tissue; this expression was significantly higher than that in normal adjacent non-carcinoma tissues. A549 cell proliferation was inhibited in all XAV939-intervention groups examined. In the wound-healing assay, cells treated with different concentrations of XAV939 exhibited a significantly increased scratch width compared with the control group. Reverse transcription-semi-quantitative polymerase chain reaction analysis revealed that β-catenin mRNA expression was significantly decreased in A549 cells in response to different XAV939 concentrations compared with the control group. Immunofluorescence revealed that β-catenin protein, initially localized in the nucleus/cytoplasm, gradually translocated to the cytoplasm/membrane, an effect that was associated with increased drug concentration. TNKS, β-catenin and c-Myc protein expression in A549 cells treated with XAV939 was reduced compared with that in untreated cells. Therefore, abnormally high TNKS expression may promote the occurrence of lung cancer. The TNKS inhibitor XAV939 inhibited lung adenocarcinoma A549 cell proliferation and migration in vitro. The underlying mechanism by which XAV939 exerted its inhibitory effects may be associated with attenuation of the WNT signaling pathway.
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影响因子：
5.2
作者：
Wu X;Luo F;Li J;Zhong X;Liu K
通讯作者：
Liu K
DOI：
10.1186/1756-9966-32-100
发表时间：
2013-12-05
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Tian XH;Hou WJ;Fang Y;Fan J;Tong H;Bai SL;Chen Q;Xu H;Li Y
通讯作者：
Li Y
影响因子：
11.8
作者：
Krishnamurthy N;Kurzrock R
通讯作者：
Kurzrock R
DOI：
10.2147/dddt.s76602
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Zhang X;Lou Y;Zheng X;Wang H;Sun J;Dong Q;Han B
通讯作者：
Han B
影响因子：
7.5
作者：
Holland, Jane D.;Klaus, Alexandra;Birchmeier, Walter
通讯作者：
Birchmeier, Walter