Anti-Tumor Activity of Stevia Leaf Extract Fermented by the Plant-Derived Lactiplantibacillus plantarum SN13T in a Pancreatic Tumor Xenograft Model

Background: Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and limited efficacy of conventional therapies. Developing safe and effective natural adjuvant therapies is therefore of considerable interest. This study evaluated the in vivo anti-tumor activity of stevia leaf extract fermented by Lactiplantibacillus (L.) plantarum SN13T in an ectopic PANC-1 xenograft mouse model and explored potential mechanisms associated with its observed biological effects. Methods: Mice with PANC-1 tumors were randomly assigned to four groups: normal saline (NC group), unfermented stevia leaf extract (SLE, Unfer group), fermented stevia leaf extract by L. plantarum SN13T (FSLE, Fer group), and capecitabine (PC group). Body weight and tumor volume were monitored throughout the experiment. At the study termination, serum, tumor, liver, and kidney samples were collected for biochemical assays, hematoxylin–eosin and immunohistochemical staining, cytokine measurements, Western blot and qPCR analyses, and antioxidant measurements. Results: Fermented stevia leaf extract significantly inhibited tumor growth, as evidenced by reduced tumor volume and weight. Serum pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) were markedly decreased, accompanied by improvement in liver injury markers (ALT, AST) and lactate dehydrogenase (LDH). In tumor tissues, FSLE was associated with increased protein expression of cleaved caspase-3 and Bax, along with decreased Bcl-2 levels. Notably, Nrf2 protein expression in tumor tissues was downregulated, while intratumoral IL-6 levels were also decreased. In the liver, treatment was accompanied by increased Nrf2 and HO-1 mRNA expression, enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels. Conclusions: FSLE exerts anti-tumor effects in a PANC-1 xenograft model that are associated with the modulation of inflammation, oxidative stress, and apoptosis-related pathways. These observations provide experimental and theoretical support for the further development of fermented plant-derived products as adjunctive therapies for pancreatic cancer.