Inhibition of proliferation and migration of melanoma cells by ketoconazole and Ganoderma immunomodulatory proteins

Lu,Chun‑Te; Leong,Pui‑Ying; Hou,Ting‑Yi; Kang,Yu‑Ting; Chiang,Yan‑Cheng; Hsu,Chih‑Ting; Lin,Yan‑De; Ko,Jiunn‑Liang; Hsiao,Yu‑Ping

doi:10.3892/ol.2019.10355

Inhibition of proliferation and migration of melanoma cells by ketoconazole and Ganoderma immunomodulatory proteins

Authors:
- Chun‑Te Lu
- Pui‑Ying Leong
- Ting‑Yi Hou
- Yu‑Ting Kang
- Yan‑Cheng Chiang
- Chih‑Ting Hsu
- Yan‑De Lin
- Jiunn‑Liang Ko
- Yu‑Ping Hsiao
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Affiliations: Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C., Department of Medical Laboratory and Biotechnology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C.
Published online on: May 14, 2019 https://doi.org/10.3892/ol.2019.10355
Pages: 891-897

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Abstract

Ketoconazole, an antifungal agent, has been used to inhibit hormone synthesis in types of prostate and breast cancer. Immunomodulatory proteins of Ganoderma microsporum (GMI) inhibit the tumor necrosis factor‑α‑ and epidermal growth factor‑induced metastatic ability of lung cancer cells. Cutaneous malignant melanoma is a highly invasive and metastatic skin cancer. However, to the best of our knowledge, there is limited understanding regarding the effects of ketoconazole and GMI on melanoma. The current study aimed to investigate the inhibitory effects of GMI combined with ketoconazole on melanoma survival and metastasis. The effects of GMI combined with ketoconazole on the viability, migration and protein expression of melanoma cells were determined by MTT assay, Boyden chamber assay and western blot analysis, respectively. The expression of monocyte chemoattractant protein‑1 (MCP‑1) was investigated by enzyme‑linked immunoabsorbent assay. The present results indicate that ketoconazole enhances the GMI‑induced decrease in proliferation and migration of A375.S2 melanoma cells in a concentration‑dependent manner. Ketoconazole was identified to reduce the level of GMI‑induced phosphorylated‑adenosine monophosphate‑activated protein kinase (p‑AMPK)‑α and autophagy; however, ketoconazole did not affect p‑AMPK‑β levels in A375.S2 cells. In addition, ketoconazole and dorsomorphin dihydrochloride, an AMPK inhibitor, were revealed to reduce MCP‑1 secretion in A375.S2 cells. In summary, the present study revealed that ketoconazole enhances GMI‑inhibited proliferation and migration of A375.S2 melanoma cancer cells, and inhibits the secretion of MCP‑1.

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