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Treatment of vemurafenib-resistant SKMEL-28 melanoma cells with paclitaxel
- Source :
- Asian Pacific journal of cancer prevention : APJCP. 16(2)
- Publication Year :
- 2015
-
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.
- Subjects :
- MAPK/ERK pathway
Proto-Oncogene Proteins B-raf
Cancer Research
Cell type
Indoles
Paclitaxel
Epidemiology
Blotting, Western
Apoptosis
Pharmacology
Immunoenzyme Techniques
chemistry.chemical_compound
Cell Movement
medicine
Cell Adhesion
Tumor Cells, Cultured
Humans
Phosphorylation
Vemurafenib
Melanoma
Cell Proliferation
Sulfonamides
Public Health, Environmental and Occupational Health
medicine.disease
Antineoplastic Agents, Phytogenic
Oncology
chemistry
Cell culture
Drug Resistance, Neoplasm
Cancer research
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 2476762X
- Volume :
- 16
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Accession number :
- edsair.doi.dedup.....a3f97345c6b36a6521b5d084f9082da7