Objective To study the effects of apigenin on proliferation, migration and angiogenesis of human melanoma A375 cells and the mechanism of action. Methods The effects of apigenin on the proliferation of A375 cells were evaluated by the MTS method, and those on the in vivo growth of melanoma were assessed by establishing a subcutaneous xenograft model of nude mice. The influence of apigenin on in vitro cell migration was detected using the scratch assay, and that on the angiogenesis of human melanoma was detected by the tube formation assay. The regulatory effects of apigenin on the expressions of proliferation- and angiogenesis-related proteins such as vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), phosphorylated p38 (p-p38), t-p38, phosphorylated ERK (p-ERK) and t-ERK were detected by Western blot. Results After in vitro treatment of A375 cells with apigenin, their in vitro proliferation and in vivo growth were significantly inhibited compared with those of the control group, and the migration capacity was also significantly lowered. Apigenin inhibited tumor cell-induced angiogenesis in the tube formation assay. Molecular mechanism study showed that apigenin inhibited the protein expressions of angiogenesis-related VEGF and MMP-9 as well as proliferation-related p-p38 and p-ERK. Conclusions Apigenin can inhibit the growth, migration and angiogenesis of melanoma A375 cells, probably by suppressing the expressions of proliferation- and angiogenesis-related proteins.

apigenin; melanoma; proliferation; migration; tumor angiogensis; molecular mechanism