Periodontitis is the most common chronic inflammatory condition occurring in the human oral cavity, but our knowledge on its contribution to oral cancer is rather limited. To define crosstalk between chronic periodontitis and oral cancer, we investigated whether Porphyromonas gingivalis, a major pathogen of chronic periodontitis, plays a role in oral cancer progression. To mimic chronic irritation by P. gingivalis in the oral cavity, oral squamous cell carcinoma (OSCC) cells were infected with P. gingivalis twice a week for 5 weeks. Repeated infection of oral cancer cells by P. gingivalis resulted in morphological changes of host cancer cells into an elongated shape, along with the decreased expression of epithelial cell markers, suggesting acquisition of an epithelial-to-mesenchymal transition (EMT) phenotype. The prolonged exposure to P. gingivalis also promoted migratory and invasive properties of OSCC cells and provided resistance against a chemotherapeutic agent, all of which are described as cellular characteristics undergoing EMT. Importantly, long-term infection by P. gingivalis induced an increase in the expression level of CD44 and CD133, well-known cancer stem cell markers, and promoted the tumorigenic properties of infected cancer cells compared to non-infected controls. Furthermore, increased invasiveness of P. gingivalis-infected OSCC cells was correlated with enhanced production of matrix metalloproteinase (MMP)-1 and MMP-10 that was stimulated by interleukin-8 (IL-8) release. This is the first report demonstrating that P. gingivalis can increase the aggressiveness of oral cancer cells via epithelial-mesenchymal transition-like changes and the acquisition of stemness, implicating P. gingivalis as a potential bacterial risk modifier.

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BackgroundKorean Red Ginseng extract (KRG, Panax ginseng Meyer) and its constituents have been used for treating diabetes. However, in diet-induced obese mice, it is unclear whether KRG can enhance the glucose-lowering action of rosiglitazone (ROSI), a peroxisome proliferator-activated receptor gamma synthetic activator.MethodsOral glucose tolerance tests (oGTTs) were performed after 4 days of treatment with a vehicle (CON), KRG [500 mg/kg body weight (b.w.)], ROSI (3.75 mg/kg b.w, 7.5 mg/kg b.w, and 15 mg/kg b.w.), or ROSI and KRG (RK) in obese mice on a high-fat diet. Adipose tissue morphology, crown-like structures (CLSs), and inflammation were compared by hematoxylin-eosin staining or quantitative reverse transcription polymerase chain reaction.ResultsThe area under the glucose curve (AUC) was significantly lower in the RK group (15 mg/kg b.w. and 500 mg/kg b.w. for ROSI and KRG, respectively) than in the CON group. There was no significant difference in the AUC between the CON and the other groups. Furthermore, the AUC was significantly lower in the RK group than in the ROSI group. The expression of the Ccl2 gene and the number of CLSs were significantly reduced in the RK group than in the CON group.ConclusionOur results show a potential enhancement of ROSI-induced improvement of glucose regulation by the combined treatment with KRG.