Tumorigenesis of smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is related to its ability to stimulate thromboxane synthase and enhance stemness of non-small cell lung cancer stem cells
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摘要Lung cancer stem cells (LCSCs) play a critical role in lung cancer development, however, it is Unknown whether thromboxane synthase (TXS) plays a role in the maintenance of LCSCs sternness. This study aimed to determine the in vivo role of TXS in lung cancer induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a smoking carcinogen. Results showed that ozagrel, a TXS blocker, suppressed NNK-induced lung tumors in mice. The expressions of CD133 and ALDH1A1 were positively associated with TXS. Similar results were observed in human NSCLC tumor samples. NNK significantly stimulated TXS and enhanced the generation of LCSCs, evident by the upregulation of CD133 and ALDH1A1 expression, and the increase in the number and size of tumor spheres. NNK also promoted the expression of LCSC-related molecules including beta-catenin and Nanog. All these NNK-mediated effects could be offset by ozagrel. In the colony formation assay, NNK increased whereas ozagrel decreased the number of colonies. Collectively, LCSCs and TXS participate in NNK-induced lung cancer. Our data suggest that TXS is a promising therapeutic target as it is a key molecular in NNK-mediated sternness of LCSCs. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
著者Liu Y, Yang SC, Li MY, Huang RY, Ng CSH, Wan IYP, Long X, Wu J, Wu B, Du J, Mok TSK, Underwood MJ, Chen GG
期刊名稱Cancer Letters
出版年份2016
月份1
日期1
卷號370
期次2
出版社ELSEVIER IRELAND LTD
頁次198 - 206
國際標準期刊號0304-3835
電子國際標準期刊號1872-7980
語言英式英語
關鍵詞Lung cancer; NNK; Smoking; Stem cells; Thromboxane
Web of Science 學科類別Oncology

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