Effect of dabrafenib on melanoma cell lines harbouring the BRAF V600D/R mutations
1 Department Melanoma, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
2 Department of Medicine, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA
3 Department of Pathology, Hospital-University Health Unit (AOU), Sassari, Italy
4 Institute of Biomolecular Chemistry, National Research Council (ICB-CNR), Sassari, Italy
5 Unit of Medical Oncology and Innovative Therapy, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, Via Mariano Semmola, 80131, Naples, Italy
BMC Cancer 2013, 13:17 doi:10.1186/1471-2407-13-17Published: 14 January 2013
Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients) appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436), has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations.
Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib.
Our experiments demonstrated an effective action of Dabrafenib (GSK2118436) and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations.
These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.