IR@PKUHSC  > 北京大学深圳医院
学科主题临床医学
Antineoplastic effects of 15(S)-hydroxyeicosatetraenoic acid and 13-S-hydroxyoctadecadienoic acid in non-small cell lung cancer
Li, Ming-Yue1; Yuan, Hui-Ling1,2; Ko, Fanny W. S.3; Wu, Bin4; Long, Xiang5; Du, Jing5; Wu, Jun4; Ng, Calvin S. H.1; Wan, Innes Y. P.1; Mok, Tony S. K.6; Hui, David S. C.3; Underwood, Malcolm J.1; Chen, George G.1
关键词15(s)-hydroxyeicosatetraenoic Acid (15(s)-hete) 13-s-hydroxyoctadecadienoic Acid (13(s)-hode) 15-lipoxygenase 1 (15-lox-1) 15-lipoxygenase 2 (15-lox-2) Lung Cancer Peroxisome Proliferator-activated Receptor (Ppar)
刊名CANCER
2015-09-01
DOI10.1002/cncr.29547
suppl.17期:SI页:3130-3145
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]ACTIVATED RECEPTOR-GAMMA ; PPAR-GAMMA ; EXPRESSION ; GROWTH ; 15-LIPOXYGENASE-2 ; APOPTOSIS ; THIAZOLIDINEDIONES ; PROGRESSION ; INHIBITION ; RADIATION
英文摘要

BACKGROUNDPrevious studies have shown that the levels of 15-lipoxygenase 1 (15-LOX-1) and 15-LOX-2 as well as their metabolites 13-S-hydroxyoctadecadienoic acid (13(S)-HODE) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) are significantly reduced in smokers with non-small cell lung carcinoma (NSCLC). Furthermore, animal model experiments have indicated that the reduction of these molecules occurs before the establishment of cigarette smoking carcinogen-induced lung tumors, and this suggests roles in lung tumorigenesis. However, the functions of these molecules remain unknown in NSCLC.

METHODSNSCLC cells were treated with exogenous 13(S)-HODE and 15(S)-HETE, and then the ways in which they affected cell function were examined. 15-LOX-1 and 15-LOX-2 were also overexpressed in tumor cells to restore these 2 enzymes to generate endogenous 13(S)-HODE and 15(S)-HETE before cell function was assessed.

RESULTSThe application of exogenous 13(S)-HODE and 15(S)-HETE significantly enhanced the activity of peroxisome proliferator-activated receptor (PPAR), inhibited cell proliferation, induced apoptosis, and activated caspases 9 and 3. The overexpression of 15-LOX-1 and 15-LOX-2 obviously promoted the endogenous levels of 13(S)-HODE and 15(S)-HETE, which were demonstrated to be more effective in the inhibition of NSCLC.

CONCLUSIONSThis study has demonstrated that exogenous or endogenous 13(S)-HODE and 15(S)-HETE can functionally inhibit NSCLC, likely by activating PPAR. The restoration of 15-LOX activity to increase the production of endogenous 15(S)-HETE and 13(S)-HODE may offer a novel research direction for molecular targeting treatment of smoking-related NSCLC. This strategy can potentially avoid side effects associated with the application of synthetic PPAR ligands. Cancer 2015;121:3130-45. (c) 2015 American Cancer Society.

语种英语
WOS记录号WOS:000360761900013
项目编号462613
资助机构Research Grants Council of the Hong Kong Special Administrative Region (Chinese University of Hong Kong)
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55824
专题北京大学深圳医院
作者单位1.Dongguan Peoples Hosp, Dept Breast Surg, Dongguan, Peoples R China
2.Peking Univ, Shenzhen Hosp, Shenzhen, Peoples R China
3.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China
4.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China
5.Guang Dong Med Coll, Affiliated Hosp, Dept Resp Med, Zhanjiang, Peoples R China
6.Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China
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Li, Ming-Yue,Yuan, Hui-Ling,Ko, Fanny W. S.,et al. Antineoplastic effects of 15(S)-hydroxyeicosatetraenoic acid and 13-S-hydroxyoctadecadienoic acid in non-small cell lung cancer[J]. CANCER,2015,suppl.17(SI):3130-3145.
APA Li, Ming-Yue.,Yuan, Hui-Ling.,Ko, Fanny W. S..,Wu, Bin.,Long, Xiang.,...&Chen, George G..(2015).Antineoplastic effects of 15(S)-hydroxyeicosatetraenoic acid and 13-S-hydroxyoctadecadienoic acid in non-small cell lung cancer.CANCER,suppl.17(SI),3130-3145.
MLA Li, Ming-Yue,et al."Antineoplastic effects of 15(S)-hydroxyeicosatetraenoic acid and 13-S-hydroxyoctadecadienoic acid in non-small cell lung cancer".CANCER suppl.17.SI(2015):3130-3145.
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