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http://dx.doi.org/10.7314/APJCP.2015.16.2.699

Treatment of Vemurafenib-Resistant SKMEL-28 Melanoma Cells with Paclitaxel  

Nguyen, Dinh Thang (Department of Biochemistry and Plant Physiology, Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University)
Phan, Tuan Nghia (Department of Biochemistry and Plant Physiology, Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University)
Kumasaka, Mayuko Y. (Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine)
Yajima, Ichiro (Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine)
Kato, Masashi (Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.2, 2015 , pp. 699-705 More about this Journal
Abstract
Vemurafenib has recently been used as drug for treatment of melanomas with $BRAF^{V600E}$ mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant $BRAF^{V600E}$ melanoma cell lines, $A375P^R$, $A375M^R$ and SKMEL-$28^R$, 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-$28^R$ cells. Treatment of SKMEL-$28^R$ 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-$28^R$ were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of $BRAF^{V600E}$-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.
Keywords
Melanoma; vemurafenib; paclitaxel; treatment resistance; $BRAF^{V600E}$; EGFR; AKT;
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