Periodontitis is a risk factor for the development of
oral squamous cell carcinomas (OSCC). Both DNA damage response (DDR) and activation of
inflammasomes induced by the microbiome might play important roles in the development of
tumors, in relation to
genome stability of
tumor cells. Herein, we explored whether
periodontitis negative-associated bacteria (Neisseria sicca and Corynebacterium matruchotii, namely called 'PNB'), which were highly abundant in healthy populations, could inhibit OSCC by promoting
genome stability. Firstly, a murine SCC-7
tumor-bearing model that colonized with PNB was designed and used in this study. Then,
cyclin D1 was detected by immunohistochemistry. Levels of DDR, NLRP3
inflammasomes and pro-inflammatory
cytokines in
tumors were detected by RT-qPCR or Western blot. Immune cells in spleens were detected by immunohistochemistry or immunofluorescence. Finally, the anti-
cancer activity of PNB was assessed in vitro using
CCK-8 assays and flow cystometry. Compared with the control, PNB decreased
tumor weights from 0.77 ± 0.26 g to 0.42 ± 0.15 g and downregulated the expression of
Cyclin D1. PNB activated the DDR by up-regulating γ-H2AX, p-ATR, and p-CHK1. PNB activated NLRP3
inflammasome-mediated pyroptosis via increases of NLRP3, gasdermin D, and
mRNA levels of apoptosis-associated speck-like
protein, Caspase-1. PNB suppressed the inflammatory response by down-regulating
mRNA levels of NF-κΒ and
IL-6 in
tumors as well as the populations of CD4+ T cells and CD206+ immune cells in spleens. PNB inhibited proliferation and promoted cell death of HSC-3 cells. In conclusion, Neisseria sicca and Corynebacterium matruchotii showed a 'probiotic bacterial' potential to inhibit OSCC by regulating
genome stability.