The Dual PI3K/mToR Inhibitor Omipalisib/GSK2126458 Inhibits Clonogenic Growth in Oncogenically-transformed Cells from Neurocutaneous Melanocytosis
| Autor: | Dipanjan Basu, Cláudia M. Salgado, Bruce S. Bauer, Yasmin Khakoo, Dominique M. Bertolini, Ryan M. Hoehl, Morgan R. Brzozowski, Janki R. Patel, Miguel Reyes-Múgica, Joie Zabec |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Programmed cell death Skin Neoplasms Apoptosis Biochemistry Melanosis 03 medical and health sciences 0302 clinical medicine Cancer stem cell Tumor Cells Cultured Genetics Humans Viability assay Clonogenic assay Melanoma Molecular Biology Protein kinase B Tumor Stem Cell Assay PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Sulfonamides Chemistry Neurocutaneous Syndromes TOR Serine-Threonine Kinases Infant Pyridazines Cell Transformation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Quinolines Cancer research Female Proto-Oncogene Proteins c-akt Signal Transduction Research Article |
| Zdroj: | Cancer Genomics - Proteomics. 15:239-248 |
| ISSN: | 1790-6245 1109-6535 |
| Popis: | Background Omipalisib has been found to affect the viability of cancer cells. However, its effect on clonogenicity - a feature of cancer stem cells, is not clear. Cells isolated from neurocutaneous melanocytosis (NCM) patients' lesions grow clonogenically. The aim of this study was to investigate the effect of omipalisib treatment on clonogenic growth of NCM cells in vitro. Materials and methods Clonogenic growth efficiency was evaluated by colony formation assays with or without specific growth factors. Activation of MEK and Akt was determined by immunoblots. Colony formation and cell viability were assessed upon pharmacological inhibition of MEK, Akt and mToR. Results Clonogenicity appeared to depend on bFGF and IGF1signaling through ERK and Akt. Omipalisib treatment prevented colony formation and induced autophagic cell death. Conclusion Signaling through Akt is important for survival of clonogenic cells in NCM, and omipalisib treatment as a monotherapy or in combination with MEK162 could be an effective therapeutic strategy to inhibit clonogenic growth. |
| Databáze: | OpenAIRE |
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