Study on the inhibitory effect of Liproxstatin-1 on the proliferation of K562 leukemia cells and its mechanism

Objective: To study the inhibitory effect of Liproxstatin-1 (Lip-1) on K562 leukemia cell line.Methods: CCK-8 method was used to detect the cell viability of different concentrations of Lip-1 before and after treatment.Untreated K562 leukemia cells were taken as control group, K562 leukemia cells treated with 10 μmol/L Lip-1 for 24 h were taken as low concentration group, and K562 leukemia cells treated with 20 μmol/L Lip-1 for 24 h were taken as high concentration group.The differences of transcriptome expression were analyzed by second generation sequencing.Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the gene and protein expressions of cyclin-dependent kinase inhibitor-1A (CDKN1A) and solute carrier family 7 member 11 (SLC7A11), respectively.Flow cytometry was used to detect the cell cycle phase.The content of glutamic acid in cells was determined by micromethod.K562 leukemia cells were cultured in medium with or without glutamine and cell counting method was used to detect cell doubling time (DT) changes.Results: Lip-1 concentration-dependent manner inhibited the proliferation of K562 leukemia cells.Compared with the control group, the gene and protein expressions of CDKN1A and SLC7A11 in low and high concentration groups increased (P＜ 0.05); the intracellular glutamicacid content in high concentration group decreased (P＜ 0.05); G1/S block occurred in low concentration group, while both G1/S and G2/M block co-existed in high concentration group.The DT of K562 leukemia cells cultured in glutamine-free medium was higher than that in glutamine-containing group (P＜ 0.05).Conclusion: Lip-1 can inhibite the proliferation of K562 leukemia cells, and its mechanism may be related to deprivation of glutamicacid acid caused by the increased expression of SLC7A11 and cell cycle arrest caused by the increased expression of CDKN1A.