NTCP (SLC10A1) has been well recognized as a basolateral (sinusoidal) Na+-bile acid co-transporter that mediates the hepatic uptake of bile acids. However, little is known about the effects of NTCP (SLC10A1) on hepatoblastoma (HB) and its underlying metabolic mechanisms. In this study, we found that NTCP (SLC10A1) expression was downregulated in HB cells and tissues, and it was demonstrated that NTCP (SLC10A1) reduced cell viability, promoted cell cycle arrest and induced apoptosis of HB cells. The metabolic profiles of HB cells with NTCP (SLC10A1) overexpression were further examined to determine their biochemical alterations and deepen our understanding on the metabolic regulation of NTCP (SLC10A1) overexpression. The metabolomics study based on ultra performance liquid chromatography-mass spectrometry revealed alterations in the metabolites of HB cells following NTCP (SLC10A1) overexpression. Next, we stably overexpressed NTCP (SLC10A1) in HepG2 cells, and found that NTCP (SLC10A1)-overexpressing cells could inhibit the production of adenosine and decreased both mRNA and protein levels of HIF1α. Further overexpression of HIF1α in the NTCP (SLC10A1)-overexpression group restored the production of adenosine. Collectively, these findings provide strong evidence that NTCP (SLC10A1) overexpression significantly disrupts the metabolism of adenosine in HB cells and highlight that NTCP (SLC10A1) mediates adenosine production mainly through HIF1α.

NTCP（SLC10A1）已被公认为介导肝脏摄取胆汁酸的基底外侧（正弦）Na +-胆汁酸共转运蛋白。但是，关于NTCP（SLC10A1）对肝母细胞瘤（HB）及其潜在代谢机制的影响知之甚少。在这项研究中，我们发现HB细胞和组织中NTCP（SLC10A1）的表达被下调，并且证明NTCP（SLC10A1）降低了细胞活力，促进了细胞周期停滞并诱导了HB细胞凋亡。进一步检查了具有NTCP（SLC10A1）过表达的HB细胞的代谢概况，以确定它们的生化改变，并加深了我们对NTCP（SLC10A1）过表达的代谢调控的了解。基于超高效液相色谱-质谱的代谢组学研究表明，NTCP（SLC10A1）过表达后，HB细胞的代谢产物发生了变化。接下来，我们在HepG2细胞中稳定地过表达NTCP（SLC10A1），发现过表达NTCP（SLC10A1）的细胞可以抑制腺苷的产生并降低HIF1α的mRNA和蛋白质水平。NTCP（SLC10A1）-过表达组中HIF1α的进一步过表达恢复了腺苷的产生。总而言之，这些发现提供了强有力的证据，表明NTCP（SLC10A1）的过表达显着破坏了HB细胞中腺苷的代谢，并突显了NTCP（SLC10A1）主要通过HIF1α介导腺苷的产生。并且发现过表达NTCP（SLC10A1）的细胞可以抑制腺苷的产生并降低HIF1α的mRNA和蛋白质水平。NTCP（SLC10A1）-过表达组中HIF1α的进一步过表达恢复了腺苷的产生。总而言之，这些发现提供了强有力的证据，表明NTCP（SLC10A1）的过表达显着破坏了HB细胞中腺苷的代谢，并突显了NTCP（SLC10A1）主要通过HIF1α介导腺苷的产生。并且发现过表达NTCP（SLC10A1）的细胞可以抑制腺苷的产生并降低HIF1α的mRNA和蛋白质水平。NTCP（SLC10A1）-过表达组中HIF1α的进一步过表达恢复了腺苷的产生。总而言之，这些发现提供了强有力的证据，表明NTCP（SLC10A1）的过表达显着破坏了HB细胞中腺苷的代谢，并突显了NTCP（SLC10A1）主要通过HIF1α介导腺苷的产生。