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 ashort period. In this study, three vemurafenib-resistant BRAFV600E melanoma cell lines, A375PR, A375MR andSKMEL-28R, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of themolecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in theRAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylationlevels of pAKTs limited to SKMEL-28R cells. Treatment of SKMEL-28R cells with 100 nM paclitaxel resultedin increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction ofexpression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-28R were decreasedby treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanismsof BRAFV600E-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested thatpaclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.