Protective Effects of Lactobacillus fermentum CQPC08 against 4-Nitroquinoline-1-Oxide–Induced Tongue Cancer in Mice

Tongue cancer is a malignant tumour originating in the anterior part of the tongue and is one of the most common malignant tumours in the oral and maxillofacial region. Lactic acid bacteria (LAB) have been of great importance in preserving vegetables, since the fermentation process results in lactic acid production, leading to a decrease in pH, which makes the environment unsuitable for the growth of microorganisms and pathogens that cause spoilage. This study investigated the in vivo chemopreventive efficacy and mechanistic actions of Lactobacillus fermentum CQPC08 (LF-CQPC08), a novel strain isolated from traditional Sichuan pickled vegetables, against experimental tongue cancer. A mouse model of tongue carcinogenesis was established using the carcinogen 4-nitroquinoline 1-oxide (4-NQO), with the commercial strain Lactobacillus delbrueckii subsp. bulgaricus serving as a comparative positive control. Biochemical analyses of serum and tissue samples revealed that LF-CQPC08 administration significantly mitigated the tumour-associated decline in systemic immunity. This was evidenced by the attenuation of reduced splenic and thymic indices, enhanced macrophage phagocytic function, and elevated serum levels of immunomodulatory factors, including granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), immunoglobulins (IgG, IgM), interleukin (IL)-4, IL-12, tumour necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). Furthermore, LF-CQPC08 treatment ameliorated oxidative stress in tongue tissues, as indicated by increased activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), coupled with a decrease in malondialdehyde (MDA) levels. At the molecular level, quantitative PCR analysis demonstrated that LF-CQPC08 upregulated the mRNA expression of cytoprotective and pro-apoptotic genes—nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione S-transferase pi (GST-π), and Bcl-2-associated X protein (Bax). Conversely, it downregulated the expression of tumour-associated genes p53, p63, p73, phosphatase and tensin homolog (PTEN), and the anti-apoptotic genes B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL). Collectively, these findings suggest that LF-CQPC08 attenuates 4-NQO–associated pathological and molecular changes in a mouse model, potentially via immunomodulatory, redox, and apoptosis-related pathways. Further studies (including validation of tumour endpoints and human studies) are required to assess translational relevance.