Treatment of vemurafenib-resistant SKMEL-28 melanoma cells with paclitaxel

Nguyen Dinh Thang, Phan Tuan Nghia, Mayuko Y. Kumasaka, Ichiro Yajima, Masashi Kato

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish
Pages (from-to)699-705
Number of pages7
JournalAsian Pacific Journal of Cancer Prevention
Volume16
Issue number2
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • AKT
  • BRAFV600E
  • EGFR
  • Melanoma
  • Paclitaxel
  • Treatment resistance
  • Vemurafenib

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

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