Abstract: PURPOSE: To investigate the effects of dihydroartemisinin(DHA) on the proliferation, apoptosis and angiogenesis of human malignant melanoma A375 cells, and to clarify its potential molecular mechanism. METHODS: Human malignant melanoma A375 cells were used as the research object, and a blank control group and DHA treatment groups with different concentrations (1, 5, 10, 20, 40, 80 μmol/L) were set up. The CCK-8 method was used to detect cell proliferation activity; flow cytometry was used to determine the cell apoptosis rate; Transwell assay was used to evaluate cell invasion ability; tube formation assay was used to detect angiogenesis ability; RT-PCR and Western blot techniques were used to detect the mRNA and protein expression levels of matrix metalloproteinase 9(MMP-9) and chemokine receptor 4 (CXCR4), respectively. RESULTS: Compared with the blank group, cell proliferation in all DHA groups with different concentrations was significantly inhibited in a dose-dependent manner. Flow cytometry analysis showed that the number of apoptotic cells in the DHA-treated groups increased significantly, and it increased with drug concentration. Transwell assay revealed that the number of cells penetrating the matrix membrane in the DHA groups was significantly reduced. The results of tube formation assay indicated that DHA could reduce the angiogenic ability of A375 cells. In addition, DHA down-regulated the mRNA and protein expressions of MMP-9 and CXCR4. CONCLUSIONS: DHA may inhibit the proliferation, invasion and angiogenesis of human malignant melanoma A375 cells and induce cell apoptosis by down-regulating the expressions of MMP-9 and CXCR4.

Key words: Dihydroartemisinin, Malignant melanoma, MMP-9, Chemokine receptor-4, Proliferation, Apoptosis, Angiogenic capacity