ArticleOncology research2025
DADS Regulates EMT and Chemotherapy Resistance by Inhibiting ROR
Article in Oncology research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Objectives: Gastric cancer (GC) is often associated with high invasiveness, epithelial-mesenchymal transition (EMT), and resistance to 5-fluorouracil (5-FU), highlighting the need for novel therapeutic targets. This study explored whether diallyl disulfide (DADS) upregulates retinoic acid-related orphan receptor alpha (RORα) to weaken the protein kinase C alpha (PKCα)/RORα-mediated RORα/β-catenin pathway, thereby inhibiting GC cell invasion, epithelial-mesenchymal transition (EMT), and enhancing 5-FU sensitivity. Methods: Human GC cell lines MGC-803 and SGC7901 were treated with DADS, RORα agonist SR1078/antagonist T0901317, and PKCα agonist TPA/antagonist GO6976. Cell proliferation (MTT), migration (scratch assay), invasion (Transwell), protein expression (Western blot), protein interactions (coimmunoprecipitation), and localization (immunofluorescence) were detected. Apoptosis and 5-FU sensitivity-related proteins were examined. Experiments were triplicated; statistics used Results: DADS/SR1078 inhibited GC cell proliferation/migration/invasion, upregulated RORα/E-cadherin, downregulated nuclear β-catenin/TGF-β1/Rac1/Vimentin, and weakened EMT (reversed by T0901317). DADS/TPA upregulated RORα/p-RORα/PKCα/p-PKCα, promoted PKCα-RORα binding, and downregulated RORα/β-catenin target genes (counteracted by GO6976). DADS upregulated caspase-3 and downregulated Bcl-2/P-gp/XIAP via RORα, promoting apoptosis and 5-FU sensitivity. Conclusion: DADS inhibits GC progression and enhances 5-FU sensitivity by PKCα/RORα-mediated downregulation of RORα/β-catenin signaling, paralleling SR1078/TPA effects. It may act as a novel RORα agonist for GC therapy.
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