Synergistic antitumor effects of circularly permuted TRAIL with doxorubicin in triple-negative breast cancer.
Acta Biochim Biophys Sin (Shanghai)
; 55(8): 1247-1256, 2023 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-37559457
ABSTRACT
Circularly permuted TRAIL (CPT), a novel recombinant TRAIL mutant, is a potent antitumor agent. However, its efficacy in triple-negative breast cancer (TNBC) remains unclear. Treatment with CPT alone and in combination with doxorubicin (Dox) is explored for its effects on the proliferation and apoptosis of MDA-MB-231 (MB231) and MDA-MB-436 (MB436) breast cancer cells in vitro and in vivo. Here, we show that CPT combined with Dox exhibits time- and dose-dependent synergy to inhibit cell viability and enhance apoptosis of MB231 and MB436 cells. Combined treatment substantially increases caspase-8, caspase-3, and PARP cleavage in both cell lines and significantly suppresses tumor growth in nude mice bearing MB231 xenografts. Collectively, our findings demonstrate that treatment with CPT in combination with Dox exerts synergistic antitumor effects through activation of the caspase cascade pathway, a mechanism that is partly dependent on the Dox-induced upregulation of death receptor 4 and death receptor 5. Therefore, CPT combined with Dox may be a feasible therapeutic strategy for the management of TNBC.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Neoplasias de Mama Triplo Negativas
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Assunto da revista:
BIOFISICA
/
BIOQUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China