Mel repressed the pro-motility and pro-angiogenesis effects of OSCC-associated neutrophils through MMP-9 suppression. (A and B) SCC-9 and SCC-25 cells were cultured in TAN-, (TAN + Mel)-, (TAN + MMP-9 inhibitor)-, (TAN + siscrb)-, or (TAN + siMMP-9)-CM for 24 h. The migration (A) and invasion (B) of SCC-9 and SCC-25 cells were evaluated by Transwell assays. The migration or invasion index of TAN-CM treatment was defined as 1. (C and D) HUVECs were cultured in TAN-, (TAN + Mel)-, (TAN + MMP-9 inhibitor)-, (TAN + siscrb)-, or (TAN + siMMP-9)-CM for 24 h. Tube formation assay was performed to measure the number of tubes (C) and branch points (D). All data represent the mean ± SD of three replicates. *P < 0.05 compared with the Ctrl group; #P < 0.05 compared with the TAN-CM group; ns: no significance compared with the TAN-CM group or (TAN + Mel)-CM group; §P < 0.05 compared with the (TAN + Mel)-CM group. CM: conditioned medium; Ctrl: control; Mel: melatonin; MMP-9 I: MMP-9 inhibitor.