Rosiglitazone inhibition of A375 human malignant melanoma cell invasion / 中华皮肤科杂志

ABSTRACT

Objective To explore the effect ofrosiglitazone (RGZ), a ligand of peroxisome proliferatoractivated receptor γ (PPARγ), on the invasiveness of A375 cells in vitro and its mechanism of action.Methods A375 human melanoma cells were cultured in vitro and treated with different concentrations of RGZ. The proliferation of the cells, mRNA expression levels of matrix metalloproteinase (MMP) 2 and tissue inhibitor of metalloproteinase (TIMP) 2, protein expression of MMP2 in A375 cells were detected by MTT assay, semi-quantitative RT-PCR and Western-blot, respectively. The invasiveness of A375 cells was detected by Matrigel invasion assay. Results MTT assay showed that the proliferation of A375 cells was inhibited by (4.86±0.31 )% and (5.15±0.52)% under the 24-hour treatment with RGZ of 10 and 25 μmol/L, respectively, and no evident cytotoxity was observed for RGZ. Compared with untreated A375 ceils, a significant decrease was observed in the mRNA and protein expression of MMP2 in A375 ceils treated with RGZ of 10 and 25 μmol/L (all P < 0.05), along with an increase in the mRNA expression of TIMP2 (both P < 0.01 ).The count of A375 cells transmigrating through matrigel was 154.1±7.7 and 87.3±8.1 under the treatment with RGZ of 10 and 25 μmol/L, significantly lower than that of those without treatment (210.7±14.9,both P < 0.01 ). Conclusions RGZ could inhibit the transmigration of A375 ceils, likely by down-regulating the mRNA and protein expression of MMP2.