Analysis of the mechanism of aldo-keto reductase dependent cis-platin resistance in HepG2 cells based on transcriptomic and NADH metabolic state

Background: Aldo-keto oxidoreductase (AKR) inhibitors could reverse the resistance of several cancer cells to cis-platin, but their role in remains unclear.Methods: We verified difference AKR1Cs expression by Western blot, RNA sequencing and qRT-PCR. The differences were analyzed inferred. Use Assay NADH NAD+ content verify inference. Docking experience was used affinity between MPA, MCFLA, MLS AKR1C3.Results: Our RNA-seq results showed de novo NAD biosynthesis-related genes NAD(P)H-dependent oxidoreductases significantly upregulated cis-platin-resistant HepG2 hepatic (HepG2-RC cells) compared with cells. At least 63 reductase/oxidases HepG2-RC at twofold. Knockdown increase cis-platin sensitivity about two-fold. Interestingly, AKR1C inhibitor meclofenamic acid eight-fold, indicating that knockdown only partially reversed resistance. Meanwhile, amount total ratio NADH/NAD+ increased almost seven-fold higher than or HL-7702 Increased be explained as a directly operating antioxidant scavenge cis-platin-induced radicals.Conclusion: report here NADH, which is produced oxidoreductases, plays key AKR-associated