Antiproliferative effect of STI571 on cultured human cutaneous melanoma-derived cell lines.
Standard antineoplastic treatment for metastatic melanoma is ineffective in the large majority of patients. Therefore, alternative approaches need to be investigated. STI571 is a new antineoplastic compound, which selectively inhibits the tyrosine kinase activity of ABL, c-Kit and platelet-derived growth factor receptor (PDGFR). Melanoma may express all of these proteins. The aim of this study was to investigate whether STI571 inhibits the in-vitro growth of melanoma cells. Nineteen cell lines were obtained from four primary and 15 metastatic melanomas of cutaneous origin. The percentages of positive cells for the putative targets of STI571 were as follows: ABL, 41-100%; c-Kit, 8-97%; PDGFR-alpha, 41-98%; PDGFR-beta, 51-99%. 3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium (MTT) and viability assays showed that STI571 clearly inhibits the proliferation of eight of the 19 (42.1%) cell lines. No relationship could be established between the expression of c-Kit, ABL, PDGFR-alpha or PDGFR-beta and the response of cell lines to STI571. Our study shows, for the first time, an antiproliferative effect of STI571 on human melanoma cell lines of cutaneous origin, raising the possibility of the future clinical use of STI571. The identification of the target of STI571 in human cutaneous melanoma cells would allow the selection of patients who could benefit from this treatment.
Department of Dermatology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
Maritza E
ME
Mayorga
Daniel
D
Sanchis
Ana M
AM
Perez de Santos
Ana
A
Velasco
Xavier
X
Dolcet
Josep M
JM
Casanova
Manel
M
Baradad
Ramon
R
Egido
Judith
J
Pallares
Noemi
N
Espurz
Daniel
D
Benitez
Jordi
J
Mila
Josep
J
Malvehy
Teresa
T
Castel
Joan X
JX
Comella
Xavier
X
Matias-Guiu
Ramon
R
Vilella
Rosa M
RM
Marti
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004252:DNA Mutational Analysis; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008545:Melanoma / Q000378:metabolism*; D016374:Oncogene Proteins v-abl / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D016374:Oncogene Proteins v-abl; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha