Pancreatic adenocarcinoma (PDAC) is a fatal malignancy and patients with PDAC are mostly diagnosed at advanced stages. Lutein is a natural compound that belongs to the non-vitamin A carotenoids family and has presented antitumor effects on multiple cancer types. However, the function of lutein in PDAC and the mechanisms are not reported. Here, we explored the role of lutein in PDAC progression. Bioinformatic analysis identified that lutein is correlated with PDAC. Lutein suppressed the proliferation, migration, and invasion of PANC-1 cells. The upregulated genes in PDAC patients were identified and the overlap analysis predicted BAG3 as one target of lutein. Lutein repressed BAG3 expression and bioinformatics analysis predicted the interaction between lutein and BAG3. The inhibitory effects of lutein on PANC-1 cell proliferation, migration, and invasion are reversed by overexpression of BAG3. GSEA analysis identified that cholesterol homeostasis as one of the downstream signaling pathways of BAG3. In conclusion, lutein induced an inhibitory effect on the malignant progression of PDAC by targeting BAG3/cholesterol homeostasis. Lutein may be applied as a promising candidate for PDAC therapy.
Keywords: BAG3; cholesterol homeostasis; lutein; network pharmacology; pancreatic adenocarcinoma.
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