Apolipoprotein B100 acts as a tumor suppressor in ovarian cancer via lipid/ER stress axis-induced blockade of autophagy
摘要Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy.As autophagy is a vital cellular process for maintaining homeostasis,targeting the autophagic pathway has emerged as an avenue for cancer therapy.In the present study,we identify apolipoprotein B100(ApoB100),a key modulator of lipid metabolism,as a potential prognostic biomarker of ovarian cancer.ApoB100 functioned as a tumor suppressor in ovarian cancer,and the knockdown of ApoB100 promoted ovarian cancer progression in vivo.Moreover,ApoB100 blocked autophagic flux,which was dependent on interfering with the lipid accumulation/endoplasmic reticulum(ER)stress axis.The effects of LFG-500,a novel synthetic flavonoid,on ApoB100 induction were confirmed using proteomics and lipidomics analyses.Herein,LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100.Moreover,data from in vivo experiments further demonstrated that ApoB100,as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy,were responsible for the anti-tumor effects of LFG-500 on ovarian cancer.Hence,our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment.
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