The reduced migration and invasion of PDT-derived variants resulted from the elevated expression and activity of histone deacetylase (HDAC). The scratch wound assay was used to examine the relative migration ability of PDT-derived A375/6A5 variants. The migration distance (µm) was measured 24 h incubated with or without 5 µM 5-AZAC (A) or 100 nM TSA (B); (C) The Matrigel invasion assay demonstrated the relative invasiveness of PDT-derived A375/6A5 cells with or without TSA treatment compared to that of parental A375 cells (200× magnification); reverse transcription PCR (RT-PCR) was used to determine the mRNA level of p300, PCAF, GCN5 (D), HDAC1, HDAC2, and HDAC3 (E) in the A375 and A375/6A5 cells. β-actin was used for normalization; (F) HDAC activity in the nuclear lysates of A375 and A375/6A5 cells was determined using a HDAC assay kit; and (G) Western blot analysis shows the levels of acetylated histone H3 in A375 and A375/6A5 cells. **, p < 0.01.