Objective To investigate the effect of cordycepin (Cor) on the chemotherapy resistance of melanoma cells by regulating the Hippo/Yes associated protein (YAP) /transcriptional coactivator with PDZ binding motif (TAZ) signaling pathway.

Methods Melanoma A375 cells and A375/ cisplatin (DDP) cells were treated with different concentrations of DDP or Cor, and cell viability was measured by CCK-8 method. A375/DDP cells were separated into control group, DDP group, DDP+Cor group, DDP+XMU-MP-1 group, and DDP+Cor+XMU-MP-1 group, cell colony formation in each group was detected, Transwell was applied to detect invasion, scratch experiment was applied to detect migration, flow cytometry was applied to detect apoptosis, Western blot was applied to detect the expression of Bax, Bcl-2, MMP-2, YAP, MST1, and TAZ proteins.

Results After DDP treatment, the viability of A375 cell was lower than A375/DDP cells (P<0.05), 33.0 μmol/L DDP was selected for the experiment; A375/DDP cells showed a gradual decrease in cell viability under different concentrations of Cor treatment (P<0.05), 200 μmol/L were selected as the experimental concentration for subsequent Cor. Compared with the control group, the number of colony formation, invasion, scratch healing rate, and the expression of YAP, MST1, TAZ, Bcl-2, and MMP-2 proteins in DDP group and DDP+Cor group significantly decreased, the apoptosis rate and Bax expression significantly increased (P<0.05). Compared with the DDP group, the trend of all indexes in DDP+Cor group was consistent, while the trend of all indexes in DDP+XMU-MP-1 group was opposite, and the differences were significant (P<0.05); XMU-MP-1 reversed the inhibitory effect of Cor on proliferation and migration of A375/DDP.

Conclusion Cor may inhibit the expression of YAP/TAZ signaling pathway proteins, inhibit cell proliferation, migration, and invasion, promote apoptosis, and reduce DDP resistance in melanoma cells.