In Vitro and In Vivo Effects of Melatonin-Containing Combination in Human Pancreatic Ductal Adenocarcinoma

Introduction: New therapeutical strategies to treat pancreatic ductal adenocarcinoma (PDAC) are necessary. Integrative therapies could potentiate the effect of anticancer drugs and reduce side effects. To date, Cannabidiol (CBD) was largely studied as anticancer in preclinical and clinical studies, while only preclinical evidence showed Melatonin (MLT) effect in different tumour models. Finally, oxygen/ozone therapy (OT) is poorly studied as anticancer treatment. Objective: The effect of MLT was evaluated in combination with CBD and OT, alone and in combination with gemcitabine in in vitro and in vivo animal models of human PDAC. Materials and methods: PANC-1 and MIAPaCa-2 human PDAC cell lines were treated with different combinations of MLT, CBD and OT, alone or with gemcitabine, and the cytotoxicity was evaluated by viability assay and cytofluorimetric analysis. Then, combinations effect was evaluated in a xenograft orthotopic PDAC mice model, evaluating both cancer volume and mass. Results: MLT, CBD, and OT combinations induced cytotoxicity and potentiated gemcitabine effect in PDAC cell lines. Moreover, in PDAC mice models, the different treatments induced a significant reduction of tumour. Conclusion: These preclinical data evidenced the combinations anticancer effect in PDAC treatment.