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

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A Correction to this article was published on 10 March 2023

A Correction to this article was published on 05 October 2022

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Abstract

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 (AMPKα) in melanoma progression through ERK signaling. The AMPKα level in melanoma tissues and cells was assessed by RT-qPCR and western blot. Survival analysis of patients with melanoma based on the AMPKα 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 AMPKα mRNA and protein levels were reduced in melanoma tissues and cells. A low expression of AMPKα indicated a poor prognosis. Functionally, itraconazole restrained melanoma cell proliferation, migration, and invasion by upregulating AMPKα. 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 AMPKα inhibited melanoma tumor growth in vivo by inhibiting ERK signaling. Itraconazole-induced AMPKα inhibits the progression of melanoma by inhibition of ERK signaling.

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Acknowledgements

We thank all participators for their help.

Funding

The work was supported by Youth Science and technology project of Zhangjiagang (ZJGQNKJ202001) and Clinical medical science and technology development fund project of Jiangsu University (JLY20180173).

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Authors and Affiliations

  1. Department of Dermatology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, Jiangsu, China

    Ni Fan, Weining Chen & Yueping Wang

  2. Department of Gynaecology and Obstetrics, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, Jiangsu, China

    Yueping Sun

  3. Center of Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, Jiangsu, China

    Lv Yan

  4. Department of General Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, Jiangsu, China

    Shusheng Wang

  5. Department of Oncology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, 215600, Jiangsu, China

    Yu Song

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  1. Ni Fan
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Correspondence to Shusheng Wang or Yu Song.

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Fan, N., Sun, Y., Yan, L. et al. Itraconazole-Induced the Activation of Adenosine 5'-Monophosphate (Amp)-Activated Protein Kinase Inhibits Tumor Growth of Melanoma via Inhibiting ERK Signaling. Cell Biochem Biophys 80, 331–340 (2022). https://doi.org/10.1007/s12013-021-01048-y

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