Evaluation of glycolytic activity and HIF-1α expression in chemoresistant colorectal cancer cells.

415 Background: Overcoming drug resistance in colorectal cancer (CRC) involves understanding the mechanisms by which cancer cells adapt to the genotoxic stress. We established a model of oxaliplatin resistant cells derived from HCT116/HT29 (HCT116 OxR/HT29 OxR). How these resistant clones reprogram their energy metabolism to gain a survival advantage remains unknown. We hypothesized that chemoresistant CRC cells exhibit altered cellular metabolism to survive following chronic genotoxic stress. Methods: The expression levels of glycolytic enzymes were detected by Western Blotting. Glucose and lactate concentrations were measured in the culturing media (CM). Intracellular ATP/ADP levels, oxygen consumption rate (OCR) and mitochondria ATP production were measured. In vivo xenograft study was used to compare the growth rate and angiogenesis of parental and oxaliplatin-resistant cells. Results: Both HT29-OxR and HCT116-OxR cells compared to parental cells exhibit increased aerobic glycolysis. Consistently, Glu...