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

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

研究成果: Article査読

10 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)699-705
ページ数7
ジャーナルAsian Pacific Journal of Cancer Prevention
16
2
DOI
出版ステータスPublished - 2015
外部発表はい

ASJC Scopus subject areas

  • 疫学
  • 腫瘍学
  • 公衆衛生学、環境および労働衛生
  • 癌研究

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