COM33 suppresses carboplatin-induced epithelial-mesenchymal transition via inhibition of Twist1 in ovarian cancer.
Acta Biochim Biophys Sin (Shanghai)
; 55(1): 34-42, 2022 Dec 25.
Article
em En
| MEDLINE
| ID: mdl-36647720
ABSTRACT
Despite favorable responses to platinum-based chemotherapy in ovarian cancer (OC), chemoresistance is still a major cause of treatment failure. Hence, we develop a novel synthetic agent, COM33, to relieve the chemoresistance caused by carboplatin. The anti-cancerous effects of the combination of COM33 and carboplatin on OC are evaluated by cell viability, wound healing, and transwell invasion assays. A mechanistic investigation is carried out by using RNA-Seq analysis and then verified by western blot analysis and immunofluorescence microscopy. The safety and efficacy in vivo are evaluated using SKOV3 tumor-bearing nude mice. Results show that the co-administration of COM33 enhances the inhibitory effects of carboplatin on cancer cell viability, migration, and invasion in vitro and tumor growth in vivo. Furthermore, COM33 suppresses the carboplatin-induced epithelial-mesenchymal transition (EMT) by inhibiting the ERK signaling pathway. Additionally, we show that Twist1, the effector of the ERK signaling pathway, participates in carboplatin-induced EMT and is also inhibited by COM33. Our data show that the combination of carboplatin with COM33 is beneficial for chemotherapy against OC, which may be a potential novel anti-tumor strategy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Resistencia a Medicamentos Antineoplásicos
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Proteína 1 Relacionada a Twist
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Transição Epitelial-Mesenquimal
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Ano de publicação:
2022
Tipo de documento:
Article