Abstract
Pancreatic cancer is one of the most lethal malignancies, characterized by late diagnosis, rapid progression, and resistance to conventional therapies. The oncogenic microRNA miR-21 is frequently upregulated in pancreatic tumors and contributes to tumor growth, migration, and chemoresistance by targeting tumor suppressor genes. Lycopene, a naturally occurring carotenoid with antioxidant and anti-inflammatory properties, has shown promise as a chemopreventive agent in several cancer types. This study investigates the therapeutic potential of lycopene in human pancreatic cancer cell lines (PANC-1 and MIA PaCa-2) and their miR-21 knockout counterparts. Treatment with 50 μM lycopene significantly reduced cell viability, colony formation, migration, and spheroid integrity and decreased intracellular reactive oxygen species (ROS) levels, with more pronounced effects in miR-21-deficient cells. These findings highlight the role of miR-21 in modulating lycopene sensitivity and support the potential of lycopene as an adjunctive therapeutic agent in pancreatic cancer.