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-κB 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. A time-course transcriptomic profiling of tumor organoids treated with CK21 in vitro

本研究旨在探究雷公藤内酯类似物CK21对胰腺癌的作用机制（Mechanism of Action, MOA）。通过对体外经CK21处理的肿瘤类器官开展时序转录组分析，结果显示：处理3小时后仅可检测到不足10个差异表达基因（differentially expressed genes, DEGs），而处理12小时后差异表达基因数量约为8000个。研究观察到全局RNA转录受到整体抑制；结合Ingenuity通路分析（Ingenuity Pathway Analysis）与细胞功能实验结果，证实CK21可抑制核因子κB（NF-κB）通路、提升氧化磷酸化水平并诱发线粒体功能异常，最终导致活性氧（reactive oxygen species, ROS）生成增加、B细胞淋巴瘤因子2（B-cell-lymphoma protein 2, BCL2）表达下调，进而引发线粒体介导的肿瘤细胞凋亡。本研究还对体外经CK21处理的肿瘤类器官开展了时序转录组分析。