Xu Fen, Zhou Xiaoyan, Hao Jian, Dai Hua, Zhang Jian, He Yuanqiao, Hao Hua
Department of General Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China.
Department of Pathophysiology, Medical College of Nanchang University, Nanchang, Jiangxi, 330006, PR China.
Prostaglandins Other Lipid Mediat. 2018 Jul;137:9-19. doi: 10.1016/j.prostaglandins.2018.05.007. Epub 2018 May 19.
Epithelial-mesenchymal Transition (EMT) and migration play an important role in tumor progression, and lipoxin (LX), the 'stop signal' for inflammation, has been studied in basic research for its anti-inflammatory or inflammatory pro-resolving properties. Here, in the in vitro experiment, we showed that LXA could inhibit the EMT and migration in phorbol myristate acetate (PMA) or activated conditioned medium (ACM)-stimulated Hep3B cells by downregulation of integrin-linked kinase (ILK), a pseudokinase in cytoplasm and these effects were via inhibiting the phosphorylation of Akt and GSK3β. Morover, LXA could not affect the EMT and migration of PMA-stimulated Hep3B cells by knockdown of ILK. In the in vivo experiment, BML-111 (the analog of LXA) could inhibit the EMT and metastasis of hepatocarcinoma cells. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3β, decreased expression of MMP-2 and MMP-9. These results showed that LXA could be a possible candidate for liver cancer therapy, and blocking ILK axis would be an effective drug target.
上皮-间质转化（EMT）和迁移在肿瘤进展中起重要作用，而脂氧素（LX）作为炎症的“终止信号”，因其抗炎或促炎症消退特性已在基础研究中得到研究。在此，在体外实验中，我们表明脂氧素A（LXA）可通过下调整合素连接激酶（ILK，一种细胞质中的假激酶）来抑制佛波酯肉豆蔻酸酯（PMA）或活化条件培养基（ACM）刺激的Hep3B细胞中的EMT和迁移，并且这些作用是通过抑制Akt和糖原合成酶激酶3β（GSK3β）的磷酸化来实现的。此外，通过敲低ILK，LXA不会影响PMA刺激的Hep3B细胞的EMT和迁移。在体内实验中，BML-111（LXA的类似物）可抑制肝癌细胞的EMT和转移。我们还证明，ILK小干扰RNA（siRNA）抑制下游信号靶点Akt和GSK3β的磷酸化，降低基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达。这些结果表明，LXA可能是肝癌治疗的一个潜在候选物，阻断ILK轴将是一个有效的药物靶点。
