Dihydromyricetin Sensitizes Drug-resistant Melanoma Cells to Carboplain Through the SIRT1/JNK Pathway

OBJECTIVE To investigate the effect and mechanisms of dihydromyricetin treatment on sensitizing carboplatin-resistant melanoma to carboplatin treatment. METHODS MTT assay was performed to evaluate the effect of dihydromyricetin and carboplatin on inhibiting the viability of carboplatin-resistant A375 (A375-R) cells. Western blot analysis was performed to detect the expression of SIRT1, activation of caspase-9 and caspase-3, and phosphorylation of JNK in the A375-R cells treated with dihydromyricetin and carboplatin. Flow cytometry analysis was performed to measure the cell apoptosis of A375-R cells treated with dihydromyricetin and carboplatin. RESULTS Results of MTT assays showed that IC₅₀ of carboplatin to A375-R was significantly higher than the A375 cells. Dihydromyricetin treatment was able to decrease the IC₅₀ of carboplatin to A375-R. Results of western blot analysis showed that expression level of SIRT1 in A375-R cells was significantly higher than that in the A375 cells. Dihydromyricetin decreased the expression of SIRT1 in A375-R. Dihydromyricetin promoted phosphorylation of JNK in A375-R cells treated with carboplatin. After transfection with SIRT1 plasmid or pretreatment with JNK specific inhibitor SP600125, dihydromyricetin plus carboplatin-induced cytotoxicity, apoptosis, activation of JNK, caspase-9 and caspase-3 was significantly suppressed. CONCLUSION Dihydromyricetin sensitizes drug-resistant melanoma cells to carboplain through the SIRT1/JNK pathway.