Activation of the NF-ĸB Signaling Pathway by Lactobacillus plantarum and Lactobacillus casei Through Modulation of TLR4 and DC-SIGN Genes in an Oral Squamous Cell Carcinoma Rat Model.

BACKGROUND: The composition of the oral and intestinal microbiota is believed to contribute to the development of oral cancer (OC). The chronic activation of pattern recognition receptors (PRRs) has been linked to the aggressive nature and poor prognosis of various cancers. Therefore, targeting PRRs has emerged as a promising strategy for cancer prevention.

AIMS: To investigate the effects of Lactobacillus plantarum (LP) and Lactobacillus casei (LC) on downstream signaling pathways of CLRs in a rat model of oral squamous cell carcinoma (OSCC).

METHODS AND RESULTS: In this study, we divided 35 rats into five groups: healthy control, cancer control, treated with live LP, treated with killed LP, and treated with live LC. Our investigation focused on gene expression of TLR4, DC-SIGN, NF-κB, and BCL2 in healthy and cancer control groups. We established a 4NQO-induced rat tongue carcinogenesis model and administered probiotic lactobacilli as a treatment. Subsequently, we re-evaluated the expression of the TLR4, DC-SIGN, NF-κB, and BCL2 genes. The antibacterial activity of both LP and LC was confirmed using the disk diffusion antibiogram method. Histopathological analysis confirmed the onset of OSCC. Expression of the NF-κB, BCL2, DC-SIGN, and TLR4 genes was significantly increased in the 4NQO treatment group compared with the control group. Our findings indicate that live and killed LP and live LC significantly reduced the expression of the NF-κB, BCL2, DC-SIGN, and TLR4 genes in cancerous rats compared with healthy rats.

CONCLUSION: Our findings suggest that the administration of LP and LC probiotics may be a promising therapeutic approach for OSCC. The LP and LC can activate the NF-ĸB signaling cascade by modulating the expression of TLR4 and DC-SIGN genes. However, further research is required to fully elucidate the mechanisms underlying these effects and determine the optimal dosage and duration of treatment.