Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair
The isolated tumor tissues and cancer cells were washed twice with precooled normal saline. To remove proteins and extract metabolites, the tissues were smashed on ice, suspended in 400 μL of precooled methanol/acetonitrile solvent mixture (MeOH/ACN = 1:1, V/V, Merck, GER), vortexed for 30 s, and then centrifuged at 12,000 × g at 4°C for 20 min. Then, the supernatant was incubated at -20°C for 1 h and dried by rotary evaporation. The samples were subsequently redissolved in 100 μL of 50% ACN solvent (ACN/H2O = 1:1, V/V) and vortexed for 30 s. After recentrifuging, the supernatant was subjected to LC‒MS analysis (AB Sciex QTRAP 6500 LC‒MS/MS platform) for metabolite detection and untargeted metabolomic profiling.
