Ionizing Radiation Increases Death Receptor 5 (DR5)-Mediated Cell Death, but Not Death Receptor 4 (DR4)-Mediated Cell Death in 3D Tumor Spheroids.

ABSTRACT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potential therapeutic for cancer patients due to its tumor specificity. However, TRAIL resistance in cancer cells limits its development in clinical trials. Given that ionizing radiation (IR) is an established method of inducing DNA damage for cancer during radiotherapy, we applied a combined treatment of IR and TRAIL. Our study shows that the combination treatment of IR and TRAIL promoted cell death due to IR upregulating both DR4/DR5 receptors on the surface of human lung carcinoma cell line H460 and human colon cancer cell line DLD-1 2D cells. However, when cultured as 3D spheroids, we observed that IR enhanced DR5-specific TRAIL-induced cell death but attenuated DR4-specific TRAIL-induced cell death. The immunoh

SUBMITTER: Suo F 

PROVIDER: S-EPMC12110968 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature