Regorafenib inhibits growth, survival and angiogenesis in nasopharyngeal carcinoma and is synergistic with Mcl-1 inhibitor.
J Pharm Pharmacol
; 75(9): 1177-1185, 2023 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-37133348
ABSTRACT
OBJECTIVES:
Regorafenib is an oral multi-kinase inhibitor approved for various metastatic/advanced cancers, and has been investigated in clinical trials in many other tumour entities. The purpose of this study was to evaluate the therapeutic potential of regorafenib for nasopharyngeal carcinoma (NPC).METHODS:
Cellular proliferation, survival, apoptosis and colony formation assays were performed and combination index was determined. NPC xenograft tumour models were established. In vitro and In vivo angiogenesis assays were performed. KEYFINDINGS:
Regorafenib is effective against a panel of NPC cell lines regardless of cellular origin and genetic profiling while sparing normal nasal epithelial cells. The predominant inhibitory effects of regorafenib in NPC are anchorage-dependent and anchorage-independent growth rather than survival. Apart from tumour cells, regorafenib potently inhibits angiogenesis. Mechanistically, regorafenib inhibits multiple oncogenic pathways including Raf/Erk/Mek and PI3K/Akt/mTOR. Regorafenib decreases Bcl-2 but not Mcl-1 level in NPC cells. The in vitro observations are evident in in vivo NPC xenograft mouse model. The combination of Mcl-1 inhibitor with regorafenib is synergistic in inhibiting NPC growth without causing systemic toxicity in mice.CONCLUSIONS:
Our findings also support further clinical investigation of regorafenib and Mcl-1 inhibitor for NPC treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Nasofaríngeas
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Pharm Pharmacol
Ano de publicação:
2023
Tipo de documento:
Article