| Autor: |
Boz Er AB; Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, University of Bradford, Bradford BD7 1DP, UK., Sheldrake HM; Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, University of Bradford, Bradford BD7 1DP, UK., Sutherland M; School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2024 Jul 20; Vol. 25 (14). Date of Electronic Publication: 2024 Jul 20. |
| DOI: |
10.3390/ijms25147946 |
| Abstrakt: |
Metastatic melanoma, a deadly form of skin cancer, often develops resistance to the BRAF inhibitor drug vemurafenib, highlighting the need for understanding the underlying mechanisms of resistance and exploring potential therapeutic strategies targeting integrins and TGF-β signalling. In this study, the role of integrins and TGF-β signalling in vemurafenib resistance in melanoma was investigated, and the potential of combining vemurafenib with cilengitide as a therapeutic strategy was investigated. In this study, it was found that the transcription of PAI1 and p21 was induced by acquired vemurafenib resistance, and ITGA5 levels were increased as a result of this resistance. The transcription of ITGA5 was mediated by the TGF-β pathway in the development of vemurafenib resistance. A synergistic effect on the proliferation of vemurafenib-resistant melanoma cells was observed with the combination therapy of vemurafenib and cilengitide. Additionally, this combination therapy significantly decreased invasion and colony formation in these resistant cells. In conclusion, it is suggested that targeting integrins and TGF-β signalling, specifically ITGA5 , ITGB3 , PAI1 , and p21 , may offer promising approaches to overcoming vemurafenib resistance, thereby improving outcomes for metastatic melanoma patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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