Midkine silencing enhances the anti-prostate cancer stem cell activity of the flavone apigenin: cooperation on signaling pathways regulated by ERK, p38, PTEN, PARP, and NF-κB.

摘要: Prostate cancer (PCa) is the most common in men worldwide. Midkine (MK) overexpressed PCa, as well tumor-initiating cells termed stem (CSCs). Apigenin a dietary flavone with considerable anti-tumor activities. In this study, we explored possible therapeutic use of MK silencing, apigenin treatment, and combination both on human PCa prostate (PCSCs). CD44+CD133+ PC3 CD44+ LNCaP CSCs were isolated from their parent cell lines. Both knockdown treatment resulted loss viability PCSCs, these effects significantly elevated when was applied silencing. Combined siRNA also more effective inducing apoptotic non-apoptotic death compared individual applications. Treatment decreased viability, although did not markedly alter therapy. Molecular events underlying cycle arrest inhibition survival, proliferation, migration found to be associated upregulated p21, p27, Bax, Bid, caspase-3, caspase-8 expression, downregulated p-p38, p-ERK, NF-κB, PARP. addition, silencing showed better outcomes anticancer efficacy docetaxel cells. conclusion, MK-regulated are different between combined plus may valuable approach for eradication PCSCs.