白杨素协同调控Alox12-GPX4/Bcl-2轴激活铁死亡抑制结直肠癌SW480细胞增殖、迁移、凋亡实验研究OA

Objective:To investigate the effects of chrysin(CHR)on proliferation,migration,and apoptosis of colorectal cancer(CRC)cells SW480 by regulating the arachidonate 12-lipoxygenase(Alox12)-glutathione peroxi-dase 4(GPX4)/B-cell lymphoma-2(Bcl-2)axis to activate ferroptosis.Methods:Potential targets of CHR were screened using network pharmacology,and molecular docking was employed to validate its binding affinity with Alox12.In the in vitro experiments,the CCK-8 assay was employed to determine the optimal drug concentrations.SW480 cells in the logarithmic growth phase were divided into the following groups:negative control(NC)group,and groups treated with 20,60μmol/L of CHR.A wound healing assay was conducted to evaluate cell migration ca-pability.The protein expression levels of GPX4 and Bcl-2 were detected by Western blot,while the mRNA level of Alox12 was analyzed using RT-qPCR.Results:Six overlapping targets related to ferroptosis,CHR,and CRC were identified.Combined with protein-protein interaction network analysis and molecular docking,Alox12 was determined as the core target of CHR in the treatment of CRC.In vitro,compared to the NC group,treatment with 60 μmol/L CHR significantly inhibited the survival and horizontal migration of CRC cells,and downregulated the expression of the ferroptosis-related protein GPX4 and the anti-apoptotic protein Bcl-2(all P<0.05).In contrast,the 20 μmol/L CHR group showed no statistically significant differences in these indicators compared to the control group(all P>0.05).Furthermore,the 60 μmol/L CHR treatment significantly increased the mRNA expression of Alox12 com-pared to the NC group(P<0.05).Conclusion:CHR can inhibit the proliferation and migration of CRC cells,and the underlying mechanism may be associated with the suppression of GPX4/Bcl-2,thereby activating the ferroptosis-ap-optosis crossover network and targeting the regulation of Alox12.