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
机构：[1]Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin N.T., Hong Kong[2]Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China[3]The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China广东省中医院[4]Peking University Shenzhen Hospital, Shenzhen, Guangdong, China北京大学深圳医院深圳医学信息中心[5]Department of Respiratory Medicine, Affiliated Hospital of Guang Dong Medical University, Zhanjiang, Guangdong, China[6]Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin N.T., Hong Kong
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.
基金：
Research Grants Council of the Hong Kong SARHong Kong Research Grants Council [CUHK475211]; CUHK direct grantChinese University of Hong Kong [2012.2.024]
第一作者机构：[1]Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin N.T., Hong Kong[2]Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China
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推荐引用方式(GB/T 7714)：
Liu Yi,Yang Shucai,Li Ming-Yue,et al.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[J].CANCER LETTERS.2016,370(2):198-206.doi:10.1016/j.canlet.2015.10.017.
APA：
Liu, Yi,Yang, Shucai,Li, Ming-Yue,Huang, Runyue,Ng, Calvin S. H....&Chen, George G..(2016).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.CANCER LETTERS,370,(2)
MLA：
Liu, Yi,et al."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".CANCER LETTERS 370..2(2016):198-206
医学