Lycopene Promotes NK Cell Cytotoxicity Towards Non-small Cell Lung Carcinoma via Regulating NF-κB Signaling

Abstract

Background: The advances in the treatment of non-small cell lung cancer (NSCLC) have yielded notable progress through targeted therapies and immunotherapies. Lycopene, a carotenoid pigment found in tomatoes, has demonstrated potential pharmacological effects, particularly in attenuating oxidative stress and inflammation. Objectives: This study aims at investigating the synergistic effects of combining lycopene with NK cell therapy to address these challenges in NSCLC treatment. Methods: Human cell lines (HUVEC, BEAS-2B, NCI-H460, and A549) were cultured, and NK cells were isolated, using a specific kit. A variety of assays, including colony formation, CCK-8, FACS detection, RT-qPCR, IFN-γ, CD107α secretion, and ELISA, were employed to assess the impact of Lycopene on NSCLC cells and NK cells both individually and in combination. Results: Lycopene exhibited limited cytotoxicity towards normal human cells and demonstrated moderate efficacy against NSCLC cells. Notably, it significantly enhanced NK cell viability and proliferation. The combination of lycopene with NK cells yielded a synergistic effect, characterized by improved killing efficiency, diminished colony formation, and elevated secretion of IFN-γ and CD107α. Mechanistically, the study explored the NF-κB signaling pathway, uncovering an upregulation of key RNA transcripts implicated in NK cell activation. Conclusions: This study provides valuable insights into the potential of integrating lycopene and NK cell therapy to enhance NSCLC treatment. The observed synergistic effects, especially the activation of the NF-κB signaling pathway, indicate a promising direction for further translational research. While acknowledging the study's limitations, including the moderate efficacy of lycopene against NSCLC cells, our findings underscore the potential of lycopene as an adjuvant in precision medicine for NSCLC. Further optimization and mechanistic investigations are necessary to fully realize the therapeutic potential of this combination.