PMID- 31289567 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 18 IP - 1 DP - 2019 Jul TI - Inhibition of proliferation and migration of melanoma cells by ketoconazole and Ganoderma immunomodulatory proteins. PG - 891-897 LID - 10.3892/ol.2019.10355 [doi] AB - 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-alpha- 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)-alpha and autophagy; however, ketoconazole did not affect p-AMPK-beta 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. FAU - Lu, Chun-Te AU - Lu CT AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. AD - Division of Plastic and Reconstructive Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C. FAU - Leong, Pui-Ying AU - Leong PY AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. AD - Department of Rheumatology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C. FAU - Hou, Ting-Yi AU - Hou TY AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. FAU - Kang, Yu-Ting AU - Kang YT AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. FAU - Chiang, Yan-Cheng AU - Chiang YC AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. AD - Department of Dermatology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C. FAU - Hsu, Chih-Ting AU - Hsu CT AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. FAU - Lin, Yan-De AU - Lin YD AD - Department of Medical Laboratory and Biotechnology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C. FAU - Ko, Jiunn-Liang AU - Ko JL AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. AD - Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C. FAU - Hsiao, Yu-Ping AU - Hsiao YP AD - Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C. AD - Department of Dermatology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C. LA - eng PT - Journal Article DEP - 20190514 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC6539804 OTO - NOTNLM OT - Ganoderma microsporum OT - adenosine monophosphate-activated protein kinase OT - ketoconazole OT - melanoma OT - monocyte chemoattractant protein-1 EDAT- 2019/07/11 06:00 MHDA- 2019/07/11 06:01 PMCR- 2019/05/14 CRDT- 2019/07/11 06:00 PHST- 2018/02/08 00:00 [received] PHST- 2019/03/07 00:00 [accepted] PHST- 2019/07/11 06:00 [entrez] PHST- 2019/07/11 06:00 [pubmed] PHST- 2019/07/11 06:01 [medline] PHST- 2019/05/14 00:00 [pmc-release] AID - OL-0-0-10355 [pii] AID - 10.3892/ol.2019.10355 [doi] PST - ppublish SO - Oncol Lett. 2019 Jul;18(1):891-897. doi: 10.3892/ol.2019.10355. Epub 2019 May 14.