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.
Original language | English |
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Pages (from-to) | 699-705 |
Number of pages | 7 |
Journal | Asian Pacific Journal of Cancer Prevention |
Volume | 16 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2015 |
Externally published | Yes |
Keywords
- AKT
- BRAFV600E
- EGFR
- Melanoma
- Paclitaxel
- Treatment resistance
- Vemurafenib
ASJC Scopus subject areas
- Epidemiology
- Oncology
- Public Health, Environmental and Occupational Health
- Cancer Research