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Medical Science Monitor Basic Research


eISSN: 1643-3750

Toll-Like Receptor 4 (TLR4)/Cyclooxygenase-2 (COX-2) Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion by NF-κB Activation

Wei Wang, Jiye Wang

Department of Urology Surgery, Tiantai People’s Hospital, Taizhou, Zhejiang, China (mainland)

Med Sci Monit 2018; 24: LBR5588-5597

DOI: 10.12659/MSM.906857

Available online: 2018-08-11

Published: 2018-08-11


BACKGROUND: Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in invasion, metastasis, and survival of various cancers. Activation of TLR4 can promote cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB). However, little is known about the effects of TLR4/COX-2 in prostate cancer (PCa).
MATERIAL AND METHODS: In our study, TLR4 and COX-2 expressions were detected by quantitative real-time reverse transcription PCR (qRT-PCR) in PCa tissues (n=34). Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and carboxyfluorescein succinimidyl ester (CFSE) assays. The migration and invasion abilities were detected by wound healing and Transwell assays. qRT-PCR and western blot assays were performed to detect TLR4, COX-2, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinases (TIMP)-1, epithelial-cadherin (E-cadherin), vimentin, NF-κB (p65), and p-p65 expressions.
RESULTS: The results revealed that TLR4 and COX-2 were upregulated in PCa tissues; Silencing of TLR4 or COX-2 inhibited PCa cell proliferation, migration, and invasion, and TLR4 siRNAs combined with COX-2 siRNAs synergistically suppressed PCa cell proliferation, migration, and invasion. Silencing of TLR4 or COX-2 also downregulated MMP-2, MMP-9, and E-cadherin expressions, and upregulated TIMP-1 and vimentin expressions. In addition, silencing of TLR4 or COX-2 inhibited p65 phosphorylation and had a synergistic effect.
CONCLUSIONS: We demonstrated that TLR4/COX-2 inhibits PCa cell proliferation, migration, and invasion by regulating NF-κB.

Keywords: Cyclooxygenase 2, NF-kappa B, Prostatic Neoplasms, Toll-Like Receptor 4, Transcellular Cell Migration