Accession Number : AD1001588


Title :   Ketone Body Metabolic Enzyme OXCT1 Regulates Prostate Cancer Chemoresistance


Descriptive Note : Technical Report,30 Sep 2013,29 Sep 2015


Corporate Author : Oregon Health and Science University Portland United States


Personal Author(s) : Liu,Qiong


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/1001588.pdf


Report Date : 01 Dec 2015


Pagination or Media Count : 14


Abstract : 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.


Descriptors :   ketones , prostate cancer , therapeutics , chemotherapy , metabolism , neoplasms , resistance


Distribution Statement : APPROVED FOR PUBLIC RELEASE