RSL3通过p38MAPK信号通路诱导子宫内膜癌细胞铁死亡的研究OA

Objective:To investigate the role of p38MAPK in ferroptosis by ferroptosis inducer RSL3 in endometrial carcino-ma HEC-1-A cells.Methods:Following treatment with the ferroptosis inducer RSL3,the proliferation inhibition rate of HEC-1-A cells was measured using the CCK-8 assay.The colony-formation ability was assessed by plate clone formation assay.Cell migra-tion,invasion,and apoptosis were evaluated via wound healing assay,Transwell experiments,and flow cytometry,respectively.Mitochondrial ultrastructural changes were observed under transmission electron microscopy.Western blot was performed to de-tect the expression of GPX4,SLC7A11,p38MAPK,and p-p38MAPK proteins following treatment with RSL3 alone or in com-bination with the ferroptosis inhibitor Ferrostatin-1(Fer-1)or the p38MAPK inhibitor(SB203580).Results:RSL3 could inhibit the proliferation,colony formation,migration and invasion and promote cell apoptosis of HEC-1-A cells(P<0.05).Transmission electron microscopy showed that RSL3 significantly shrunk the volume of mitochondria,increased the density of membrane,and reduced the cristoid.Western blot results showed that the expressions of ferroptosis-related proteins GPX4 and SLC7A11 were sig-nificantly decreased after RSL3 intervention,and the expression of p-p38MAPK protein was increased,while the expression of p38MAPK protein was not significantly changed.The combination of Fer-1 and RSL3 can reverse the down-regulation effect of RSL3 on GPX4 and SLC7A11 expression at protein level;Compared to RSL3,the combination of SB203580 and RSL3 signifi-cantly decreased the protein expression of p-p38 and increased the protein expression of GPX4 and SLC7A11(P<0.05).Conclu-sion:RSL3 can induce ferroptosis,inhibit cells proliferation and promote apoptosis in HEC-1-A cells by activating p38MAPK sig-naling pathway.