Itraconazole-Induced the Activation of Adenosine 5′-Monophosphate (Amp)-Activated Protein Kinase Inhibits Tumor Growth of Melanoma via Inhibiting ERK Signaling

Itraconazole, an effective broad-spectrum antifungal drug, has been well established for its anticancer activity in cancers including melanoma. However, details concerning its underlying mechanism in melanoma are unclear. This work investigated the function of itraconazole-induced 5'-monophosphate (AMP)-activated protein kinase alpha (AMPK alpha) in melanoma progression through ERK signaling. The AMPK alpha level in melanoma tissues and cells was assessed by RT-qPCR and western blot. Survival analysis of patients with melanoma based on the AMPK alpha expression level was performed according to TCGA database. Melanoma cell proliferation, migration, and invasion were examined using CCK-8, colony formation, wound healing, and Transwell assays. A xenograft tumor model was established to examine the effect of itraconazole on tumor growth in vivo. The AMPK alpha mRNA and protein levels were reduced in melanoma tissues and cells. A low expression of AMPK alpha indicated a poor prognosis. Functionally, itraconazole restrained melanoma cell proliferation, migration, and invasion by upregulating AMPK alpha. Itraconazole activated AMPK signaling and inhibited ERK signaling in melanoma cells. Activation of ERK signaling reversed the effect of itraconazole on cellular process in melanoma. Moreover, itraconazole-induced AMPK alpha inhibited melanoma tumor growth in vivo by inhibiting ERK signaling. Itraconazole-induced AMPK alpha inhibits the progression of melanoma by inhibition of ERK signaling.