Parthenolide Enhances Cisplatin Sensitivity in Uveal Melanoma by Regulated Mitogen-Activated Protein Kinase Signal Pathway

Abstract

To investigate parthenolide (PTL)’s effect to cisplatin (DDP) sensitivity in uveal melanoma and to show the underlying mechanism. Human uveal melanoma cell line M23 was split into the control group, PTL treatment group, DDP treatment group, PTL + DDP treatment group, DDP + Mitogen-activated protein kinase (MAPK) signal inhibitor (SB203580) treatment group, and PTL + DDP + MAPK signal activator (anisomycin) treatment group. CCK-8 test was conducted to detect cell viability, flow cytometry was utilized for cell apoptosis detection, and western blot was utilized to determine the phosphorylation of p38MAPK and JNK. Compared to the control group, PLT treatment group M23 cell activity, and expression of p-p38MAPK, p-JNK were reduced notably (P < 0.05). Meanwhile, these indices of DDP treatment group were lower than of the control group but higher than of the PTL treatment group. In the PTL + DDP treatment group M23 cell activity and expression level of p-p38MAPK, p-JNK was significantly lower than in the PTL and DDP treatment groups (P < 0.05). Inhibition of MAPK signal pathway increased the DDP effect to proliferation inhibition and apoptosis promotion. In contrast, MAPK signal pathway activator treatment alleviates PTL + DDP treatment effect on M23 cell line apoptosis and proliferation. Parthenolide (PTL) increased cisplatin (DDP) sensitivity in uveal melanoma through the inhibition of MAPK signal pathway.