Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells.

Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In the present study, we explored the correlation between AFP regulation of macrophage function and the possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) and monocytes from healthy donors were used to analyze the effect of AFP on the macrophages' phenotype and phagocytosis. THP-1 cells and healthy human donor-derived monocytes were polarized into M0 macrophages induced by phorbol ester (PMA), and M0 macrophages were polarized into M1 macrophages induced by lipopolysaccharide(LPS) and interferon-γ(IFN-γ). Interleukin-4(IL-4) and interleukin-13(IL-13) were used to induce M0 macrophage polarization into M2 macrophages. Tumor-derived AFP(tAFP) stimulated M0 macrophage polarization into M2 macrophages and inhibited M1 macrophages to phagocytize HCC cells. The role of AFP in promoting macrophage polarization into M2 macrophages and inhibiting the M1 macrophages to phagocytize HCC cells may be involved in activating the PI3K/Akt signaling pathway. AFP could also enhanced the migration ability of macrophages and inhibited the apoptosis of HCC cells when co-cultured with M1-like macrophages. AFP is a pivotal cytokine that inhibits macrophages to phagocytize HCC cells.

α-Fetoprotein fragment synergizes with sorafenib to inhibit hepatoma cell growth and migration and promote the apoptosis.

Alpha fetoprotein (AFP) is associated with hepatocellular carcinoma (HCC) by stimulating the proliferation, metastasis and drug resistance. The application of AFP fragments to inhibit the malignant behaviours induced by AFP is a new strategy for the treatment of HCC. In an effort to design, screen and discover drugs, we attempted to express different human AFP fragments (AFP220-609 , AFP390-609 and AFP460-609 ) in a Bac-to-Bac system. We found that the AFP390-609 fragment was highly expressed in the system. Then, we assessed the bioactivity of the fragment in the human liver cancer cell line Bel7402, and the results indicated that the AFP fragment synergized with sorafenib to inhibit the hepatoma cell growth and migration and promote the apoptosis. This study provides a method to produce significant AFP fragments to screen AFP inhibitors for use in HCC therapy.