Yang Lin, Ma Cui, Zhang Lixin, Zhang Min, Li Fei, Zhang Chen, Yu Xiufeng, Wang Xiaoying, He Siyu, Zhu Daling, Song Yinli
Central Laboratory of Harbin Medical University (Daqing), PR China; Department of Pathology and Pathophysiology, College of Basic Medical Science, Harbin Medical University (Daqing), PR China; Department of Nursing, Daqing Medical College, PR China.
Central Laboratory of Harbin Medical University (Daqing), PR China; College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), PR China.
Prostaglandins Other Lipid Mediat. 2018 Sep;138:31-40. doi: 10.1016/j.prostaglandins.2018.07.003. Epub 2018 Aug 12.
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 transwell 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.
15-脂氧合酶-2（15-LOX-2）和15（S）-羟基二十碳四烯酸（15（S）-HETE）被认为是包括癌症在内的多种生物过程的潜在介质。然而，它们在肺腺癌（LAC）中的功能尚不清楚。在本研究中，我们旨在确定15-LOX-2/15（S）-HETE是否参与A549细胞的增殖和迁移，并确定参与该过程的信号通路。我们使用免疫组织化学来鉴定肺癌组织样本中15-LOX-2的表达水平。通过细胞活力测定、免疫荧光、蛋白质印迹、划痕试验和Transwell试验评估15（S）-HETE在缺氧条件下对A549细胞增殖和迁移的影响。我们发现，与相邻正常组织样本相比，LAC组织样本中15-LOX-2的表达显著上调。缺氧条件下A549细胞中15（S）-HETE的含量增加。此外，15（S）-HETE可刺激增殖细胞核抗原（PCNA）、细胞周期蛋白A和细胞周期蛋白D的表达。此外，15-LOX-2的小干扰RNA（siRNA）在体外抑制了A549细胞的增殖和迁移。我们的数据还提供了新的证据，证明信号转导和转录激活因子3（STAT3）通路参与了15（S）-HETE诱导的A549细胞增殖和迁移。本研究可能有助于更深入地了解LAC转移，并为15（S）-HETE/STAT3通路与该疾病相关的机制提供新的线索。
