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Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma
Published on: March 13, 2013
Antiproliferative effect of STI571 on cultured human cutaneous melanoma-derived cell lines
Maritza E Mayorga1, Daniel Sanchis, Ana M Perez de Santos
1Department of Dermatology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.
Abstract:
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.
Insights
Standard treatments for metastatic melanoma are often ineffective. This study found that STI571, a tyrosine kinase inhibitor, demonstrated antiproliferative effects on some human melanoma cell lines, suggesting potential clinical applications.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Metastatic melanoma frequently resists standard antineoplastic therapies.
- Novel therapeutic strategies are crucial for improving patient outcomes.
- STI571 targets tyrosine kinases ABL, c-Kit, and platelet-derived growth factor receptor (PDGFR), which may be expressed in melanoma.
Purpose of the Study:
- To evaluate the in-vitro antiproliferative activity of STI571 against human melanoma cell lines.
- To determine if melanoma cell expression of ABL, c-Kit, or PDGFR correlates with sensitivity to STI571.
Main Methods:
- Nineteen melanoma cell lines (four primary, 15 metastatic) were utilized.
- Expression levels of ABL, c-Kit, PDGFR-alpha, and PDGFR-beta were assessed.
- Cell proliferation was measured using MTT and viability assays after STI571 treatment.
Main Results:
- STI571 inhibited the proliferation of 8 out of 19 (42.1%) melanoma cell lines.
- Expression of ABL, c-Kit, PDGFR-alpha, or PDGFR-beta did not correlate with STI571 response.
- This study provides the first evidence of STI571's antiproliferative effect on human cutaneous melanoma cells.
Conclusions:
- STI571 exhibits antiproliferative activity against a subset of human melanoma cell lines.
- Further research is needed to identify the specific molecular targets mediating STI571's effect in melanoma.
- Identifying responsive patients could enable future clinical application of STI571 in melanoma treatment.

