Department of Oncology Medilcal Center, The First People's Hospital of Zhaoqing, Zhaoqing, Guangdong, 526000, China.
Department of Interventional, First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu, 215006, China.
Lipids Health Dis. 2021 Jul 25;20(1):74. doi: 10.1186/s12944-021-01486-w.
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.
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）治疗移植性肝癌（HCC）结局的影响。
建立移植性 HCC 大鼠模型。然后，将大鼠随机分为四组：假手术组、TACE 组、维替泊芬（Hippo/YAP 抑制剂）组和 TACE+维替泊芬组。将 Lent-OE-YAP 转染入大鼠体内以过表达 YAP。治疗后，分析不同组大鼠的形态变化、肿瘤重量和总体生存率。实时 PCR、免疫组织化学染色和 Western blot 用于确定与 Hippo/YAP 信号通路相关的因子的表达。
与 Sham 组相比，TACE 组和维替泊芬组的肿瘤重量和组织病变明显减轻。维替泊芬显著降低 TACE 治疗后的肿瘤重量。此外，维替泊芬显著改善了 TACE 治疗后移植性 HCC 大鼠的总体生存率。与 Sham 组相比，TACE 组和维替泊芬组的巨噬细胞刺激因子（MST）1、MST2、长效甲状腺刺激素 1、含 PDZ 结合基序的转录共激活因子（TAZ）、Yes 相关蛋白（YAP）、TEA 结构域转录因子（TEAD）1、TEAD2、TEAD3 和 TEAD4 的表达均显著降低。TACE 联合维替泊芬显著增强了 Hippo/YAP 信号通路效应物的下调作用，减少了肿瘤体积，而过表达 YAP 则产生了相反的效果。
通过维替泊芬抑制 Hippo/YAP 信号通路显著改善了 TACE 治疗移植性 HCC 的结局。
