{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:09:42Z","timestamp":1787062182989,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T00:00:00Z","timestamp":1534118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Medical University Beigang Hospital","award":["CMUBH R106-002"],"award-info":[{"award-number":["CMUBH R106-002"]}]},{"name":"Ministry of Science and Technology, Taipei, Taiwan","award":["105-2815-C-039-082-B"],"award-info":[{"award-number":["105-2815-C-039-082-B"]}]},{"name":"Experiments and data analysis were performed in part through the use of the Medical Research Core Facilities Center, Office of Research &amp; Development at China Medical University, Taichung, Taiwan, R.O.C.","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Many studies have demonstrated that berberine inhibited the cell migration and invasion in human cancer cell lines. However, the exact molecular mechanism of berberine inhibiting the cell migration and invasion of human melanoma A375.S2 and A375.S2\/PLX (PLX4032 induced resistant A375.S2) skin cancer cells remains unknown. In this study, we investigated the anti-metastasis mechanisms of berberine in human melanoma cancer A375.S2 cells and A375.S2\/PLX resistant cells in vitro. Berberine at low concentrations (0, 1, 1.5 and 2 \u03bcM) induced cell morphological changes and reduced the viable cell number and inhibited the mobility, migration, and invasion of A375.S2 cells that were assayed by wound healing and transwell filter. The gelatin zymography assay showed that berberine slightly inhibited MMP-9 activity in A375.S2 cells. Results from western blotting indicated that berberine inhibited the expression of MMP-1, MMP-13, E-cadherin, N-cadherin, RhoA, ROCK1, SOS-1, GRB2, Ras, p-ERK1\/2, p-c-Jun, p-FAK, p-AKT, NF-\u03baB, and uPA after 24 h of treatment, but increased the PKC and PI3K in A375.S2 cells. PLX4032 is an inhibitor of the BRAFV600E mutation and used for the treatment of cancer cells harboring activated BRAF mutations. Berberine decrease cell number and inhibited the cell mobility in the resistant A375.S2 (A375.S2\/PLX, PLX4032 generated resistant A375.S2 cells). Based on these observations, we suggest that the potential of berberine as an anti-metastatic agent in melanoma that deserves to be investigated in more detail, including in vivo studies in future.<\/jats:p>","DOI":"10.3390\/molecules23082019","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T11:27:13Z","timestamp":1534159633000},"page":"2019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via Affecting the FAK, uPA, and NF-\u03baB Signaling Pathways and Inhibits PLX4032 Resistant A375.S2 Cell Migration In Vitro"],"prefix":"10.3390","volume":"23","author":[{"given":"Jia-Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-1222","authenticated-orcid":false,"given":"Kuang Chi","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan"},{"name":"Department of Surgery, China Medical University Beigang Hospital, Beigang, Yunlin 65152, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Fen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5937-0917","authenticated-orcid":false,"given":"Pornsuda","family":"Maraming","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nursing, St. Mary\u2019s Junior College of Medicine, Nursing and Management, Yilan 26644, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Shin","family":"Chueh","sequence":"additional","affiliation":[{"name":"Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-2287","authenticated-orcid":false,"given":"Jing-Gung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Biotechnology, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,13]]},"reference":[{"key":"ref_1","first-page":"120","article-title":"Epidemiology of skin cancer","volume":"810","author":"Leiter","year":"2014","journal-title":"Adv. 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