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 journalArticlepeer-review

10 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
Externally publishedYes

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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