Enhanced antitumor immunity in breast cancer: Synergistic effects of ADAM10/ADAM17 inhibition, metabolic modulation, and camptothecin-loaded selenium nanoparticles

• Published in: International journal of pharmaceutics 2024-12, Vol.669, p.125037, Article 125037
• Main Authors: Entezam, Mahshad, Bagheri, Nader, Soltani, Amin, Hosseini, Sayedeh Azimeh, Khosravian, Pegah, Ferns, Gordon A., Ghatrehsamani, Mahdi
• Format: Article
• Language: English
• Subjects: Breast cancer; Camptothecin; CD8+ T cell; GW280264X; Metformin
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.125037

[Display omitted] In this study, we investigate the impact of a multi-targeted therapeutic approach that includes camptothecin (CPT), a potent chemotherapeutic topoisomerase inhibitor; metformin (Met), a metabolic modulator with emerging anti-tumor effects; and GW280264X, an inhibitor of ADAM 10/ADAM 17 enzymes, which are associated with tumor invasion and immune response. The study aims to assess the combined effects of these agents in enhancing CD8+ T cell-mediated anti-tumor immunity and suppressing cancer cell growth in triple-negative breast cancer (TNBC) models, both in vitro and in vivo. Cell viability was performed on the 4 T1 human TNBC cell line. Furthermore, we examined c-MYC protein expression by western blot, TOX and NR4A expression by Real-time PCR, and the number of CD8+ CD28+ T cells by immunofluorescence assay to demonstrate the anticancer effects of combined of CPT, Met and GW280264X in BC growth, exhaustion and senescence of T cells. Regarding cell viability, HA-Se@CPT + Met and HA-Se@CPT + Met + GW280264X treatments decreased 4 T1 cell growth (p