Canagliflozin Modulates Hypoxia-Induced Metastasis, Angiogenesis and Glycolysis by Decreasing HIF-1α Protein Synthesis via AKT/mTOR Pathway.

ABSTRACT: The microenvironment plays a vital role in tumor progression, and hypoxia is a typical microenvironment feature in nearly all solid tumors. In this study, we focused on elucidating the effect of canagliflozin (CANA), a new class of antidiabetic agents, on hepatocarcinoma (HCC) tumorigenesis under hypoxia, and demonstrated that CANA could significantly inhibit hypoxia-induced metastasis, angiogenesis, and metabolic reprogramming in HCC. At the molecular level, this was accompanied by a reduction in VEGF expression level, as well as a reduction in the epithelial-to-mesenchymal transition (EMT)-related proteins and glycolysis-related proteins. Next, we focused our study particularly on the modulation of HIF-1α by CANA, which revealed that CANA decreased HIF-1α protein level by inhibiting its

SUBMITTER: Luo J 

PROVIDER: S-EPMC8704642 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature