Lipoxin A4 and its analog suppress hepatocellular carcinoma via remodeling tumor microenvironment.

Macrophages play an important role in tumor inflammatory microenvironment, lipoxin (LX), the 'stop signal' for inflammation, has been extensively studied preclinically for its anti-inflammatory or inflammatory pro-resolving effect. Here, we showed that LXA(4) could promote the apoptosis and inhibit the proliferation, migration and angiogenesis of HepG2 hepatocarcinoma cells stimulated by lipopolysaccharide (LPS) or activated macrophage-conditioned media (ACM). Moreover, BML-111, the analog of LXA(4), effectively inhibited the proliferation, invasion and angiogenesis of tumor in H22 hepatocarcinoma cell bearing mice. These results showed that LXA(4) could be a possible candidate for liver cancer therapy, and blocking the activation of macrophages would be an effective drug target.