Porphyromonas gingivalis-OMVs promote the epithelial-mesenchymal transition of oral squamous cell carcinoma by inhibiting ferroptosis through the NF-κB pathway.

Abstract

Background: Recent studies reported the role of Porphyromonas gingivalis (P. g) in promoting oral squamous cell carcinoma (OSCC) progression. However, the molecular mechanism remains unclear.

Materials and methods: P. g-OMVs were isolated using ultracentrifugation method and characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). CCK-8, migration, invasion, Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and immunocytochemistry assays were performed to evaluate the effect of P. g-OMVs on tumor cells' proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and ferroptosis in vitro. Western blot was performed to study the phosphorylation of transcription factor nuclear factor kappa B (NF-κB). In vivo, the effect of P. g-OMVs on the growth of OSCC was evaluated using a xenograft tumor model, followed by hematoxylin and eosin and immunohistochemistry staining.

Results: TEM and NTA demonstrated that P. g-OMVs have a vesicular structure with a particle size of around 118 nm. Compared to the control group, P. g-OMVs significantly enhance the proliferation, migration, and invasion of tumor cells. In addition, P. g-OMVs promote the EMT of OSCC cells, which can be attenuated by ferroptosis activator erastin. Moreover, P. g-OMVs inhibit feroptosis of OSCC by activating NF-κB signaling. In vivo, P. g-OMVs significantly enhance tumor growth of OSCC. Inhibition of NF-κB could significnatly reduce the growth of OSCC, which can be further rescued using ferroptosis inhibitor Ferrostain-1.

Conclusions: P. g-OMVs promote OSCC progression by modulating the ferroptosis-related EMT through NF-κB signaling.