Lipoxin A4 and its analog suppress hepatocarcinoma cell epithelial-mesenchymal transition, migration and metastasis via regulating integrin-linked kinase axis

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 LXA4 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, LXA4 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 LXA4) 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 LXA4 could be a possible candidate for liver cancer therapy, and blocking ILK axis would be an effective drug target.