A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma

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.

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

“…The expression level of uPA or miR-23 in MM samples was measured using qPCR following the methods described in previous publications and instructions from the manufactures ( 28 – 30 ). Briefly, RNA samples of MM cells or tumor tissues were extracted using a PARISTM Kit (Thermo Fisher Scientific, Waltham, MA, USA).…”

DHW-208, A Novel Phosphatidylinositol 3-Kinase (PI3K) Inhibitor, Has Anti-Hepatocellular Carcinoma Activity Through Promoting Apoptosis and Inhibiting Angiogenesis

“…PI3K signaling pathway plays a key role in tumor angiogenesis by regulating the expression of HIF-1α and VEGF. Activation of the PI3K/AKT/mTOR pathway in tumor cells can also increase VEGF secretion, both by hypoxia-inducible factor 1 dependent and independent mechanisms ( 11 ). Numerous inhibitors targeting the PI3K/AKT/mTOR pathway have been developed, and these agents have been shown to decrease VEGF secretion and angiogenesis ( 70 ).…”

“…In the past few years, immunotherapy has made some progress in treating cancer, and Atezolizumab/Bevacizumab is the first and only immunotherapy with a proven benefit in HCC (8)(9)(10). However, the treatment options for advanced HCC are still very limited (11,12). Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation and remains the representative approved systemic treatment for advanced HCC (13,14).…”

Knockdown of TANK-Binding Kinase 1 Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular-Targeted Drugs

“…The cell lines used in this study were mainly liver-derived, non-tumor cell lines (L-02) and some HCC cell lines (including MHCC97-H, MHCC97-L, HepG2, Huh-7, BEL-7402, and SMMC-7721). These cell lines are maintained in our laboratory and detailed in previous publications ( He X et al, 2021 ; Yang H et al, 2021 ; Jiang Q et al, 2021 ; Li et al, 2021 ). The expression levels assessed in these experiments included the full-length sequence of TBK1 and its siRNA, which were prepared as the lentivirus (these were transduced into lentivirus vectors).…”