Fig. 6: The histone lactylation/NEDD4/PTEN axis plays an important role in 5-Fu-resistant cells.

A IC50 values of 5-Fu-sensitive (Ctrl) and 5-Fu-resistant strains (Res) in Lm3 and Huh7 cells. (The dashed line represents the drug concentration at which 50% of cells survive.) B Intracellular lactate production in 5-Fu-sensitive (Ctrl) and 5-Fu-resistant (Res) cells. (The dashed line represents the drug concentration at which 50% of cells survive.) C Western blot analysis of changes in PKla and H3K14la protein levels after oxamate treatment. D Changes in NEDD4 protein levels in 5-Fu-resistant cells (Res) under si-EP300, oxamate, and lactate treatments. E PTEN and NEDD4 protein levels were detected by western blotting. F Immunofluorescence confirmed the increased colocalization of PTEN and NEDD4 in 5-Fu-resistant cells, scale bar = 10 µm. The X-axis represents the pixel intensity of NEDD4 (red), and the Y-axis represents the pixel intensity of PTEN (green). G Colocalization was quantified using ImageJ (n = 3). H Detection of PTEN ubiquitination levels after Co-IP with PTEN in 5-Fu-sensitive (Ctrl) and resistant (Res) cells. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.