Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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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)
  • Published : 2015.02.25
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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

References

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