Hepatocellular carcinoma (HCC) was the third most common cause of cancer death. But it has only limited therapeutic options, aggressive nature, and very low overall survival. Dihydroartemisinin (DHA), an anti-malarial drug approved by the Food and Drug Administration (FDA), inhibited cell growth in HCC. The Warburg effect was one of the ten new hallmarks of cancer. Solute carrier family 2 member 1 (SLC2A1) was a crucial carrier for glucose to enter target cells in the Warburg effect. Yes-associated transcriptional regulator 1 (YAP1), an effector molecule of the hippo pathway, played a crucial role in promoting the development of HCC. This study sought to determine the role of DHA in the SLC2A1 mediated Warburg effect in HCC. In this study, DHA inhibited the Warburg effect and SLC2A1 in HepG2215 cells and mice with liver tumors in situ. Meanwhile, DHA inhibited YAP1 expression by inhibiting YAP1 promoter binding protein GA binding protein transcription factor subunit beta 1 (GABPB1) and cAMP responsive element binding protein 1 (CREB1). Further, YAP1 knockdown/knockout reduced the Warburg effect and SLC2A1 expression by shYAP1-HepG2215 cells and Yap1^LKO mice with liver tumors. Taken together, our data indicated that YAP1 knockdown/knockout reduced the SLC2A1 mediated Warburg effect by shYAP1-HepG2215 cells and Yap1^LKO mice with liver tumors induced by DEN/TCPOBOP. DHA, as a potential YAP1 inhibitor, suppressed the SLC2A1 mediated Warburg effect in HCC.

肝细胞癌 (HCC) 是癌症死亡的第三大常见原因。但它只有有限的治疗选择、侵略性和非常低的总体生存率。双氢青蒿素 (DHA) 是一种经美国食品和药物管理局 (FDA) 批准的抗疟疾药物，可抑制 HCC 中的细胞生长。Warburg 效应是癌症的十大新标志之一。溶质载体家族 2 成员 1 (SLC2A1) 是 Warburg 效应中葡萄糖进入靶细胞的关键载体。Yes-associated transcriptional regulator 1 (YAP1) 是河马通路的效应分子，在促进 HCC 的发展中起着至关重要的作用。本研究旨在确定 DHA 在 HCC 中 SLC2A1 介导的 Warburg 效应中的作用。在这项研究中，DHA 抑制了 HepG2215 细胞和原位肝肿瘤小鼠中的 Warburg 效应和 SLC2A1。同时，DHA 通过抑制 YAP1 启动子结合蛋白 GA 结合蛋白转录因子亚基 beta 1 (GABPB1) 和 cAMP 反应元件结合蛋白 1 (CREB1) 来抑制 YAP1 表达。进一步，YAP1敲低/敲除降低了shYAP1 -HepG2215 细胞和患有肝肿瘤的Yap1 ^{LKO小鼠的 Warburg 效应和 SLC2A1 表达。}总之，我们的数据表明，YAP1敲低/敲除降低了shYAP1 -HepG2215 细胞和Yap1 ^LKO小鼠对 DEN/TCPOBOP 诱导的肝肿瘤的 SLC2A1 介导的 Warburg 效应。DHA 作为一种潜在的 YAP1 抑制剂，可抑制 HCC 中 SLC2A1 介导的 Warburg 效应。