Abstract
BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation. A series of HCC tumor models were established to determine not only the sustained release of microcrystalline BAY-876, but also its long-acting antitumor activity. The clinical role of BAY-876 was confirmed by the increased expression of GLUT1, which was associated with the worse prognosis among advanced HCC patients. A single dose of injection of microcrystalline BAY-876 directly in the HCC tissue achieved sustained localized levels of Bay-876. Moreover, the single injection of microcrystalline BAY-876 in HCC tissues not only inhibited glucose uptake and prolonged proliferation of HCC cells, but also inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors. Thus, the microcrystalline BAY-876 described in this study can directly achieve promising localized effects, given its limited diffusion to other tissues, thereby reducing the occurrence of potential side effects, and providing an additional option for advanced HCC treatment.
Highlights
Despite the current progress of hepatocellular carcinoma (HCC)-related research, the overall prognosis of advanced HCC is still poor [1, 2]
The liver is a pivotal organ responsible for the body’s energy metabolism and the excessive uptake of glucose by HCC cells is the key to abnormal metabolism, a mechanism which is mediated by glucose transporters (GLUT) [6,7,8,9]
The Glucose transporter type 1 (GLUT1) expression in a larger cohort of HCC patients was examined by using the data from TCGA or GTEx
Summary
Despite the current progress of hepatocellular carcinoma (HCC)-related research, the overall prognosis of advanced HCC is still poor [1, 2]. It is valuable to identify new therapeutic agents for intervention in advanced HCC treatment targeting the GLUTs. GLUT1 (Glucose transporter type 1) is the most common member of the GLUTs and is widely expressed in adult organs. GLUT1 (Glucose transporter type 1) is the most common member of the GLUTs and is widely expressed in adult organs Under stress factors such as hypoxia, low partial pressure of oxygen, and changes in osmotic pressure, cells can uptake a large amount of glucose through GLUT1 to meet the body’s energy metabolism requirements [10,11,12]. The aim of this study was to establish a long-acting and sustained-release formulation of BAY-876 to achieve precise dose administration, and exert targeted anti-tumor activity at HCC lesions without affecting normal tissues and organs. As the size of the microcrystals is larger and the release is slower
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
