Novel Imidazo[2,1-b]oxazole Derivatives Inhibit Epithelial Cell Transformation and Triple Negative Breast Cancer Tumorigenesis.
Anticancer Res
; 40(9): 5081-5090, 2020 Sep.
Article
em En
| MEDLINE
| ID: mdl-32878796
ABSTRACT
BACKGROUND/AIM:
Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with limited targets for chemotherapy. This study evaluated the inhibitory effects of novel imidazo[2,1-b]oxazole-based rapidly accelerated fibrosarcoma (RAF) inhibitors, KIST0215-1 and KIST0215-2, on epithelial cell transformation and TNBC tumorigenesis. MATERIALS ANDMETHODS:
Immunoblotting, BrdU incorporation assay, reporter gene assay, and soft agar assay analyses were performed. In vivo effects were studied using the BALB/c mouse xenograft model.RESULTS:
KIST0215-1 and KIST0215-2 inhibited the RAFs-MEK1/2-ERK1/2 signalling pathway induced by EGF in MDA-MB-231 cells, which inhibited c-fos transcriptional activity and activator protein-1 transactivation activity. KIST0215-1 and KIST0215-2 also prevented neoplastic transformation of JB6 C141 mouse epidermal cells induced by EGF and consistently suppressed the growth of tumours formed by 4T1 cells in BALB/c mice.CONCLUSION:
Inhibition of RAF kinases using KIST0215-1 and KIST0215-2 is a promising chemotherapeutic strategy to treat TNBC.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
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Transição Epitelial-Mesenquimal
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Neoplasias de Mama Triplo Negativas
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Imidazóis
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Antineoplásicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article