title: Treatment of vemurafenib-resistant SKMEL-28 melanoma cells with paclitaxel.
abstract: Vemurafenib has recently been used as drug for treatment of melanomas with BRAFV600E mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant BRAFV600E melanoma cell lines, A375PR, A375MR and SKMEL-28R, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-28R cells. Treatment of SKMEL-28R cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-28R were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of BRAFV600E-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.
authors: Department of Biochemistry and Plant Physiology, Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University, Hanoi, Vietnam E-mail : ndthang@hus.edu.vn.
authors: Nguyen Dinh
authors: ND
authors: Thang
authors: Phan Tuan
authors: PT
authors: Nghia
authors: Mayuko Y
authors: MY
authors: Kumasaka
authors: Ichiro
authors: I
authors: Yajima
authors: Masashi
authors: M
authors: Kato
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D007211:Indoles / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000077484:Vemurafenib
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf; D017239:Paclitaxel