Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines
<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is a highly chemotherapy resistant tumour. The use of newer targeted therapies alone and in combination with chemotherapy may offer new hope of improving response to treatment. Dasatinib, a multi-target kinase inh...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-09-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/6/1/53 |
| _version_ | 1828950370967093248 |
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| author | Clynes Martin Crown John Eustace Alex J O'Donovan Norma |
| author_facet | Clynes Martin Crown John Eustace Alex J O'Donovan Norma |
| author_sort | Clynes Martin |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is a highly chemotherapy resistant tumour. The use of newer targeted therapies alone and in combination with chemotherapy may offer new hope of improving response to treatment. Dasatinib, a multi-target kinase inhibitor, is currently approved for the treatment of chronic myeloid leukaemia and has shown promising results in preclinical studies in a number of solid tumours.</p> <p>Methods</p> <p>We examined the effects of dasatinib on proliferation, chemo-sensitivity, cell cycle arrest, apoptosis, migration and invasion in human melanoma cell lines. Expression and activation of Src kinase, FAK and EphA2 were also examined in the melanoma cells.</p> <p>Results</p> <p>Dasatinib inhibited growth of three of the five melanoma cell lines. Comparison with sorafenib showed that in these three cell lines dasatinib inhibited growth at lower concentrations than sorafenib. Dasatinib in combination with the chemotherapy drug temozolomide showed greater efficacy than either drug alone. Dasatinib induced cell cycle arrest and apoptosis and significantly inhibited cell migration and invasion of melanoma cells. Dasatinib inhibition of proliferation was associated with reduced phosphorylation of Src kinase, while decreased phosphorylation of FAK was implicated in dasatinib-mediated inhibition of migration and invasion in melanoma cells.</p> <p>Conclusion</p> <p>Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma.</p> |
| first_indexed | 2024-12-14T06:22:40Z |
| format | Article |
| id | doaj.art-64f1b6590617481bb9f0c1dc70c137b0 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T06:22:40Z |
| publishDate | 2008-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-64f1b6590617481bb9f0c1dc70c137b02022-12-21T23:13:46ZengBMCJournal of Translational Medicine1479-58762008-09-01615310.1186/1479-5876-6-53Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell linesClynes MartinCrown JohnEustace Alex JO'Donovan Norma<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is a highly chemotherapy resistant tumour. The use of newer targeted therapies alone and in combination with chemotherapy may offer new hope of improving response to treatment. Dasatinib, a multi-target kinase inhibitor, is currently approved for the treatment of chronic myeloid leukaemia and has shown promising results in preclinical studies in a number of solid tumours.</p> <p>Methods</p> <p>We examined the effects of dasatinib on proliferation, chemo-sensitivity, cell cycle arrest, apoptosis, migration and invasion in human melanoma cell lines. Expression and activation of Src kinase, FAK and EphA2 were also examined in the melanoma cells.</p> <p>Results</p> <p>Dasatinib inhibited growth of three of the five melanoma cell lines. Comparison with sorafenib showed that in these three cell lines dasatinib inhibited growth at lower concentrations than sorafenib. Dasatinib in combination with the chemotherapy drug temozolomide showed greater efficacy than either drug alone. Dasatinib induced cell cycle arrest and apoptosis and significantly inhibited cell migration and invasion of melanoma cells. Dasatinib inhibition of proliferation was associated with reduced phosphorylation of Src kinase, while decreased phosphorylation of FAK was implicated in dasatinib-mediated inhibition of migration and invasion in melanoma cells.</p> <p>Conclusion</p> <p>Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma.</p>http://www.translational-medicine.com/content/6/1/53 |
| spellingShingle | Clynes Martin Crown John Eustace Alex J O'Donovan Norma Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines Journal of Translational Medicine |
| title | Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines |
| title_full | Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines |
| title_fullStr | Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines |
| title_full_unstemmed | Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines |
| title_short | Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines |
| title_sort | preclinical evaluation of dasatinib a potent src kinase inhibitor in melanoma cell lines |
| url | http://www.translational-medicine.com/content/6/1/53 |
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