| Autor: |
Qian Zhao, Hong-Ping Zhu, Xin Xie, Qing Mao, Yan-Qing Liu, Xiang-Hong He, Cheng Peng, Qing-Lin Jiang, Wei Huang |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
International Journal of Molecular Sciences, Vol 21, Iss 5, p 1845 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1422-0067 |
| DOI: |
10.3390/ijms21051845 |
| Popis: |
Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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