Oral microbiota member Neisseria elongata exosomes-Cassia fistula association targets PTEN/AKT/IL10/IL1β/BAX/BCL-2 signaling pathway in pancreatic cancer immunotherapy

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Abstract
Pancreatic cancer, characterized by its aggressive progression and limited therapeutic options, remains a malignancy with high mortality rates. This study evaluates the potential of bacterial extracellular vesicles (EVs) as immunotherapeutic carriers, focusing on Neisseria elongata-derived exosomes conjugated with a methanol extract of Cassia fistula, a plant with known anticancer properties. The cytotoxic and apoptotic effects of this complex were systematically analyzed using the PANC-1 pancreatic cancer cell line. MTT and LDH assays revealed a concentration-dependent reduction in cell viability and enhanced cytotoxicity. Mechanistic analyses demonstrated upregulation of pro-apoptotic BAX/BCL-2 ratio and modulation of PTEN/AKT signaling pathways, indicating activation of intrinsic apoptosis. Furthermore, increased levels of the pro-inflammatory cytokine IL-1β and suppression of anti-inflammatory IL-10 suggested immunomodulatory effects. Elevated reactive oxygen species (ROS) levels corroborated the induction of oxidative stress-mediated apoptosis. These results underscore the dual functionality of Neisseria elongata exosomes as both drug carriers and biological response modifiers. The biocompatibility and targeting efficiency of bacterial EVs position them as a novel therapeutic platform for gastrointestinal cancers. This study provides the first preclinical evidence supporting the use of non-pathogenic bacterial exosomes in oncology, highlighting their translational potential for improving treatment outcomes in pancreatic cancer.

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