KH3 inhibited PDAC cell growth by reducing glycolysis and mitochondrial respiration via targeting PGAM1. (A) KH3 suppressed the proliferation of PDAC cell lines and PDAC primary cells isolated from patients. (B) Knockdown of PGAM1 impaired the inhibition of KH3 (1 μM) on proliferation of PANC-1 cells when compared to control. Knockdown of PGAM1 in PANC-1 cells was verified by Western blot. (C) KH3 suppressed glycolysis of PANC-1 cells. (D) KH3 suppressed mitochondrial respiration of PANC-1 cells. (E) Cell energy phenotype of PANC-1 cells was altered after KH3 treatment. The data were presented as mean ± SD (n = 5), and P values were obtained from unpaired t test (n.s., not significant. *: 0.01 < P < 0.05, **: 0.001 < P < 0.01, ***: 0.0001 < P < 0.001, ****P < 0.0001). OCR, oxygen consumption rate; ECAR, extracellular acidification rate; XF, seahorse XF system.