Unresolved
inflammation, due to insufficient production of proresolving anti-inflammatory
lipid mediators, can lead to
tumorigenesis. Among these mediators,
lipoxin A4 (
LXA4) has potent anti-carcinogenic properties, and may serve as key target for modulating
inflammation-associated
cancer like
colorectal cancer. The purpose of present study was to clarify the roles of
LXA4 in
colorectal cancer. We investigated the effects and underlying mechanisms of
LXA4 in
colorectal cancer and its relationship with
tumor-associated
inflammation and immune microenvironment by employing clinical samples and mouse
colorectal cancer cell line CT26-bearing
tumor model as well as
colorectal cancer cells. It was found that
colorectal cancer is associated with dysregulation of immune microenvironment and deficiency of
LXA4 that could play different roles at different stages of
tumor growth: inhibiting early but promoting late
tumor growth. Analysis of peripheral immune cells in subcutaneous xenograft mice model disclosed that early
LXA4 treatment induced lymphocytes and inhibited neutrophils and monocytes, while late
LXA4 treatment induced neutrophils but inhibited lymphocytes. Detailed analysis of tumor microenvironment revealed that early
LXA4 treatment could inhibit inflammatory mediators expressions and leukocytes infiltration into
tumor. Furthermore,
LXA4 could suppress the expressions of p-ERK, p-P38 and NF-κB in subcutaneous xenograft. Additionally,
LXA4 could inhibit the proliferation and migration of
colorectal cancer cells, and, meanwhile, inhibit the proliferation and migration of
colorectal cancer cells stimulated by activated macrophage-
conditioned media. These findings suggest that
colorectal cancer is associated with a deficiency of
LXA4 that could suppress
colorectal cancer via modulating
tumor-associated
inflammation and immune microenvironment as well as inhibiting
colorectal cancer cell development.