Fig. 5: AKR1B1-mediated fructose production from glucose played an extremely important role in the proliferation of cancer cells both in vitro and in vivo.

A Impaired proliferation for AKR1B1-KO cells as relative to NC cells. Cells were cultured in high glucose DMEM medium containing 10% FBS (n = 3). B Fructose supplementation recovered the proliferation of AKR1B1-KO cells. Cells were cultured in glucose-free DMEM medium containing 10% dialyzed FBS and 5 mM of glucose, supplemented with the indicated concentration of fructose for 4 days (A549 group: n = 6, U87 group: n = 3). C, D The images showing compromised colony formation in AKR1B1-KO cells, which was rescued by exogenous provision of fructose at 10 mM (C). Bar plots on the right side revealing the quantitative and statistical results (D). Cells were cultured in glucose-free DMEM medium containing 20% dialyzed FBS and 5 mM of glucose. Every 48 h, as indicated, the spent medium was exchanged with fresh media. After 14 days, the cells were fixed by 4% paraformaldehyde and stained with crystal violet for colony formation analysis (n = 3). AKR1B1-KO retarding the expansion of A549 (E) and U87 (F) xenograft tumors (n = 8). The negative impact of AKR1B1-KO on tumor volume and tumor weight of A549 (G) and U87 (H). Data are represented as mean ± SEM. *: t test P < 0.05; #: t test P < 0.01.