Triptolide analogs induced apoptosis on pancreatic cancer patient-derived organoids

Investigate the MOA of triptolide analog-CK21 in pancreatic cancer. Time course transcriptomic profiling of tumor organoids treated with CK21 in vitro revealed <10 differentially expressed genes (DEGs) at 3 h and ~8,000 DEGs at 12 h. Overall inhibition of general RNA transcription was observed, and Ingenuity pathway analysis together with functional cellular assays confirmed inhibition of the NF-?B pathway, increased oxidative phosphorylation and mitochondrial dysfunction, leading ultimately to increased reactive oxygen species (ROS) production, reduced B-cell-lymphoma protein 2 (BCL2) expression, and mitochondrial-mediated tumor cell apoptosis. Overall design: A time-course transcriptomic profiling of tumor organoids treated with CK21 in vitro