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• W2939357844 abstract "ABSTRACT Nimotuzumab is a humanized anti‐EGF monoclonal antibody that has been approved for treating different cancers. However, few studies have examined its therapeutic potential in prostate cancer (PC), a most common and highly aggressive malignancy among male population. We used both LNCaP, and PC3 and PC3‐AR (androgen receptor) cells as the model system and assessed the effects of nimotuzumab on epithelial–mesenchymal transition (EMT) in vitro and in vivo . The EMT makers were detected by immunohistochemistry, qRT‐PCR and Western blot. MTT, wound healing assay, and transwell assay were used to measure cell viability, migration, and invasion, respectively. For mechanistic understanding, we evaluated the significance of Akt/Y‐box binding protein‐1 (YB‐1)/AR axis in nimotuzumab‐induced EMT by overexpressing AR, activating Akt using SC79, and/or downregulating YB‐1 using siRNA. Nimotuzumab suppressed the xenograft growth from both LNCaP and PC3 cells in vivo , which was associated with reduced EMT. Consistently, nimotuzumab inhibited proliferation, cell‐cycle progression, EMT, and migration/invasion, but stimulated apoptosis of both LNCaP and PC3‐AR cells in vitro . On the molecular level, nimotuzumab inactivated Akt and YB‐1 and reduced the expression of AR. Boosting AR expression in LNCaP and PC3‐AR cells antagonized the action of nimotuzumab, at least partially restored EMT, and enhanced the migration/invasion. We also found that Akt was essential for controlling YB‐1 activation, and both critical for regulating the levels of AR and EMT‐related biomarkers. In this study, we presented our novel findings that by targeting the Akt/YB‐1/AR axis, nimotuzumab significantly inhibited EMT of PC cells. Considering that EMT is a critical mechanism contributing to the metastatic spread of cancer cells, nimotuzumab may become a promising therapy for alleviating the malignant progression of PC. © 2019 IUBMB Life, 1–14, 2019" @default.
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• W2939357844 date "2019-03-25" @default.
• W2939357844 modified "2023-10-05" @default.
• W2939357844 title "Nimotuzumab inhibits epithelial–mesenchymal transition in prostate cancer by targeting the Akt/YB‐1/AR axis" @default.
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• W2939357844 doi "https://doi.org/10.1002/iub.2028" @default.
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