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). 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. 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. The inhibition of the Hippo/YAP signaling pathway via verteporfin significantly improved the outcomes of TACE in treating transplanted HCC.

中文翻译：

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经导管动脉化疗栓塞联合Hippo/YAP抑制剂显着提高移植肝细胞癌大鼠的生存率

本研究旨在探讨抑制Hippo/Yes相关蛋白(YAP)信号通路对经导管动脉化疗栓塞(TACE)治疗移植性肝细胞癌(HCC)疗效的影响。建立移植的HCC大鼠模型。然后，将大鼠随机分为四组：Sham、TACE、维替泊芬（Hippo/YAP抑制剂）和TACE+维替泊芬。将 Lent-OE-YAP 转染到大鼠体内以在体内过表达 YAP。对治疗后不同组大鼠的形态学变化、肿瘤重量及总生存期进行分析。采用实时荧光定量 PCR、免疫组化染色和蛋白质印迹法检测 Hippo/YAP 信号通路相关因子的表达。与 Sham 组相比，TACE 组和维替泊芬组的肿瘤重量和组织病变显着减少。Verteporfin 在 TACE 治疗后显着降低了肿瘤重量。此外，维替泊芬显着提高了 TACE 治疗后移植 HCC 大鼠的总体存活率。与 Sham 组相比，TACE 和维替泊芬组的巨噬细胞刺激 (MST)1、MST2、长效甲状腺刺激素 1、具有 PDZ 结合基序 (TAZ) 的转录共激活因子 (TAZ)、Yes 相关蛋白的表达均显着降低(YAP)、TEA 结构域转录因子 (TEAD)1、TEAD2、TEAD3 和 TEAD4。TACE 加维替泊芬显着增强了 Hippo/YAP 信号通路中效应物的下调并减小了肿瘤大小，而 YAP 的过表达则产生了相反的作用。