RETRACTED: Melatonin Inhibits Migration and Invasion in LPS-Stimulated and -Unstimulated Prostate Cancer Cells Through Blocking Multiple EMT-Relative Pathways (Retracted Article)

Purpose: Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin. Materials and Methods: DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze beta-catenin ubiquitination. Results: Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial-mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-kappa B/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKT(ser473) and GSK-3 beta(ser9). Moreover, LPS induced phosphorylation of GSK-3 beta(ser9) in the "disruption complex", and then inhibited phosphorylation and ubiquitination of cytoplasmic beta-catenin, leading to beta-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3 beta and beta-catenin pathways. Conclusion: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.