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Lipids Health Dis ; 20(1): 74, 2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34304741

RESUMO

BACKGROUND: This study aimed to explore the effect of inhibiting the Hippo/Yes-associated protein (YAP) signaling pathway on the outcomes of transcatheter arterial chemoembolization (TACE) in treating transplanted hepatocellular carcinoma (HCC). METHODS: A transplanted HCC rat model was established. Then, rats were randomly divided into four groups: Sham, TACE, verteporfin (inhibitor of Hippo/YAP), and TACE+verteporfin. Lent-OE-YAP was transfected into rats to overexpress YAP in vivo. After treatments, morphological changes, tumor weight, and the overall survival of rats in different groups were analyzed. Real-time PCR, immunohistochemistry staining, and Western blotting were used to determine the expression of factors related to the Hippo/YAP signaling pathway. RESULTS: Tumor weight and tissue lesions in the TACE and verteporfin groups were significantly reduced compared with the Sham group. Verteporfin significantly decreased tumor weight after TACE treatment. In addition, verteporfin significantly improved the overall survival of rats with transplanted HCC after TACE treatment. Compared with the Sham group, both TACE and verteporfin groups exhibited significantly decreased expression of macrophage-stimulating (MST)1, MST2, long-acting thyroid stimulator 1, transcriptional co-activator with PDZ-binding motif (TAZ), Yes-associated protein (YAP), TEA domain transcription factor (TEAD)1, TEAD2, TEAD3, and TEAD4. TACE plus verteporfin significantly enhanced the downregulation of effectors in the Hippo/YAP signaling pathway and decreased tumor size, while the overexpression of YAP exerted opposite effects. CONCLUSION: The inhibition of the Hippo/YAP signaling pathway via verteporfin significantly improved the outcomes of TACE in treating transplanted HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Via de Sinalização Hippo/efeitos dos fármacos , Neoplasias Hepáticas/terapia , Verteporfina/uso terapêutico , Animais , Western Blotting , Carcinoma 256 de Walker , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Neoplasias Hepáticas/mortalidade , Masculino , Transplante de Neoplasias , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Serina-Treonina Quinase 3/antagonistas & inibidores , Proteínas de Sinalização YAP/antagonistas & inibidores
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