胰腺导管腺癌（PDAC）预后差，死亡率高。因此，有必要寻找新的靶点和治疗策略来改善PDAC患者的预后。综合疗法越来越多地被用来提高已知抗癌治疗方法的功效。因此，本研究旨在使用人体体外和体内模型来评估不同潜在抗癌分子、褪黑激素 (MLT)、大麻二酚 (CBD) 和氧臭氧 (O2/O3) 的新型组合对治疗 PDAC 的效果。 PDAC。与用于 PDAC 治疗的最常见化疗药物吉西他滨 (GEM) 联合研究了该组合的效果。 MLT  CBD  O2/O3 组合在抑制 PDAC 细胞活力和增殖、诱导细胞死亡以及调节 RAS 途径蛋白水平方面比单独治疗更有效。此外，不同的治疗组合减少了 PDAC 小鼠模型中的肿瘤质量，从而促进了 GEM 的效果。总之，MLT  CBD  O2/O3 的混合物可以作为 PDAC 的潜在辅助治疗策略。© 2024 作者。约翰·威利出版的《松果体研究杂志》

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen-ozone (O2/O3) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O2/O3 was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O2/O3 could serve as a potential adjuvant therapeutic strategy for PDAC.© 2024 The Author(s). Journal of Pineal Research published by John Wiley & Sons Ltd.