WITHDRAWN: The TLR4/MyD88/NF-κB pathway promotes infl ammation in HPV-related cervical cancer cells

Abstract

// Ninghong Jiang 1,2 , Feng Xie 1,2 , Qisang Guo 1,2 , Limei Chen 1,2 , Fang Chen 1,2 , Luopei Guo 1,2 and Long Sui 1,2 1 Medical center for diagnostics and treatments of cervical disease, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China 2 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China Correspondence to: Long Sui, email: suilong@fudan.edu.cn Keywords : cervical carcinoma; HPV; TLR4/NF-κB signaling pathway; infl ammation; tumor promotion Received: July 18, 2017 Accepted: January 02, 2018 Epub: January 08, 2018 Abstract Toll-like receptor 4 (TLR4) promotes proinfl ammatory cytokine production and activation of innate immunity. It is also highly expressed in human papillomavirus (HPV)-related cervical cancer. In our study, we investigated the role of the TLR4/MyD88/NF-κB pathway in HPV-related cervical cancer. RT-qPCR and western blotting were used to detect mRNA and protein levels in HeLa and CaSki cells. Levels of IL-6, IL-8, IL-1β, VEGF, TGF-β1, IFN-α, MIP-3α and TNF-α in cell supernatants were detected using ELISAs. Expression levels of MyD88, IRAK1, IRAK4, TRAF-6 and MAPK as well as phosphorylation of IKKα/IKKβ, IκBα and p65 were all higher than control in LPS-stimulated groups of HeLa and CaSKi cells. By contrast, lower expression was detected in groups transfected with shRNA targeting TLR4, though expression of IKKα/IKKβ, IκBα and p65 remained unchanged. Levels of COX-2, iNOS,MIP-3α, IL-6, IL-8, VEGF and TGF-β1 were higher in LPS-stimulated than in negative control groups, but were lower in cells transfected with TLR4-shRNA.These data suggest the TLR4/MyD88/NF-κB pathway promotes expression of proinfl ammatory cytokines in HPVrelated cervical cancer cells, which involves in the formation of microenvironment for tumor development. Targeting the TLR4/MyD88/NF-κB pathway can provide a rationale for treatment of HPV-related cervical cancer.