Ketone Body Metabolic Enzyme OXCT1 Regulates Prostate Cancer Chemoresistance

: OXCT1 is a key enzyme in ketone body metabolism and cellular energy homeostasis. Analysis of patient data indicated that higher OXCT1 levels are associated with docetaxel chemotherapy resistance. In order to investigate the role of OXCT1 in prostate cancer chemotherapy resistance and the underlying mechanisms, we established OXCT1 stable knock down prostate cancer cell lines. The results revealed that lowering OXCT1 level using shRNA knock down increased docetaxel chemosensitivity in prostate cancer cells. Lowering OXCT1 enhanced docetaxel induced JNK signaling pathway activation and downstream apoptotic signaling. OXCT1 knock down increased ADP/ATP, NAD+/NADH and oxygen consumption in docetaxel treated cells compared to control knock down cells, therefore induced metabolic inefficiency. These results confirmed our hypothesis that OXCT1 plays important role in prostate cancer chemotherapy sensitivity and revealed the mechanisms.