15-Lipoxygenase-2/15(S)-hydroxyeicosatetraenoic acid regulates cell proliferation and metastasis via the STAT3 pathway in lung adenocarcinoma

被引:13
|
作者
Yang, Lin [1 ,4 ,7 ]
Ma, Cui [1 ,2 ]
Zhang, Lixin [1 ,2 ]
Zhang, Min [1 ,3 ]
Li, Fei [1 ,4 ]
Zhang, Chen [3 ]
Yu, Xiufeng [1 ,2 ]
Wang, Xiaoying [1 ,3 ]
He, Siyu [1 ,3 ]
Zhu, Daling [1 ,3 ,5 ,6 ]
Song, Yinli [4 ]
机构
[1] Harbin Med Univ Daqing, Cent Lab, Xinyang Rd 39, Daqing 163319, Heilongjiang, Peoples R China
[2] Harbin Med Univ Daqing, Coll Med Lab Sci & Technol, Daqing, Heilongjiang, Peoples R China
[3] Harbin Med Univ, Coll Pharm, Harbin, Heilongjiang, Peoples R China
[4] Harbin Med Univ Daqing, Coll Basic Med Sci, Dept Pathol & Pathophysiol, Xinyang Rd 39, Daqing 163319, Heilongjiang, Peoples R China
[5] State Prov Key Labs Biomed Pharmaceut China, Shanghai, Peoples R China
[6] Harbin Med Univ, Minist Educ, Key Lab Cardiovasc Med Res, Harbin, Heilongjiang, Peoples R China
[7] Daqing Med Coll, Dept Nursing, Daqing, Peoples R China
基金
中国国家自然科学基金;
关键词
Lung adenocarcinoma; 15-Lipoxygenase-2/15(S)-Hydroxyeicosatetraenoic acid; Signal transducer and activator of transcription 3; Hypoxia; Proliferation; CANCER METASTASIS; HYPOXIA; ACTIVATION; RECEPTOR; INHIBITION; EXPRESSION; GROWTH; 15-LIPOXYGENASES; INVASION;
D O I
10.1016/j.prostaglandins.2018.07.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
15-Lipoxygenase-2 (15-LOX-2) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) have been considered as latent mediators of diverse biological processes including cancer. However, their functions in lung adenocarcinoma (LAC) are unclear. In this study, we aimed to determine whether 15-LOX-2/15(S)-HETE is involved in the proliferation and migration of A549 cells and to identify the signaling pathways that participate in this process. We used immunohistochemistry to identify the expression levels of 15-LOX-2 in lung cancer tissue samples. The effects of 15(S)-HETE on the proliferation and migration of A549 cells under hypoxic conditions were assessed by cell viability assays, immunofluorescence, western blotting, scratch wound assays and trans well assays. We found that the expression of 15-LOX-2 was significantly up-regulated in LAC tissue samples compared with adjacent normal tissue samples. The content of 15(S)-HETE in A549 cells was increased under hypoxic conditions. Moreover, 15(S)-HETE could stimulate the expression of PCNA, cyclin A and cyclin D. In addition, siRNA of 15-LOX-2 inhibited the proliferation and migration of A549 cells in vitro. Our data also provide novel evidence demonstrating that the STAT3 pathway participates in the 15(S)-HETE-induced proliferation and migration of A549 cells. This study may provide a greater understanding of LAC metastasis and shed new light on the mechanisms by which the 15(S)-HETE/STAT3 pathway is related to this disease.
引用
收藏
页码:31 / 40
页数:10
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