Temporal regulation of HIF-1 and NF-κB in hypoxic hepatocarcinoma cells Temporal regulation of HIF-1 and NF-κB in hypoxic hepatocarcinoma cells

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Clinical and laboratory studies have suggested that multi-targeting approaches against neoplastic cells could help to increase patient survival and might reduce the emergence of cells that are resistant to single-target inhibitors. Artesunate (ART) is one of the most potent and rapidly acting antimalarial agents known, and it also exerts a profound cytotoxic activity toward cancer cells and reverses multi-drug resistance. In the present study, we found that artesunate inhibited NSCLC A549 cell growth and proliferation, induced apoptosis and suppressed tumor growth in a dose-dependent manner in A549 cells and a mouse xenograft model. Furthermore, artesunate down-regulated the expression of epidermal growth factor receptor (EGFR), Akt and ATP-binding cassette subfamily G member 2 (ABCG2) at the mRNA and protein levels in vitro and in vivo. In conclusion, artesunate is an effective anti-cancer drug that may enhance the effectiveness of other anticancer drugs and may reverse multi-drug resistance by suppressing the transcription of ABCG2, which inhibits drug efflux.

Fibrinogen-like protein 2 (Fgl2) is critical for immune regulation in the inflammatory state. Elevated Fgl2 levels are observed in patients with inflammatory bowel disease (IBD), but little is known about its functional significance. In this study, we sought to investigate the role of Fgl2 in the development of intestinal inflammation and colitis-associated colorectal cancer (CAC). Here, we report that Fgl2 deficiency increased susceptibility to dextran sodium sulfate-induced colitis and CAC in a mouse model. During colitis development, the expression of the membrane-bound and secreted forms of Fgl2 (mFgl2 and sFgl2, respectively) in the colon were increased and predominantly expressed by colonic macrophages. In addition, using bone marrow chimeric mice, we determined that Fgl2 function in colitis is strictly related to its expression in the hematopoietic cells. Loss of Fgl2 induced the polarization of M1, but suppressed that of M2 both in vivo and in vitro, independent of intestinal inflammation. Thus, Fgl2 suppresses intestinal inflammation and CAC development through its role in macrophage polarization and may serve as a therapeutic target in inflammatory diseases, including IBD.