Effects of cyclic acute and chronic hypoxia on the expression levels of metabolism related genes in a pancreatic cancer cell line

Abstract

The aim of this study was to characterize cycling hypoxia-induced changes in the expression of metabolism-related genes in the pancreatic cancer cell line PANC1. PANC1 cells were exposed to either 7 h cycles of hypoxia every other day for 20 cycles (cyclic acute hypoxia), or for 72 h cycles of hypoxia once a week for 5 cycles (cyclic chronic hypoxia). Changes in gene expression were profiled using reverse transcription-quantitative PCR and compared to cells cultured under normoxic conditions. Western blotting analysis confirmed upregulation of HIF1-α, glucose-6-phosphate isomerase, and ribokinase at the mRNA level. Upregulation in genes encoding enzymes involved in glycolysis was greater in cells cultured under cyclic acute hypoxia compared with cells cultured under chronic hypoxia including hexokinase2 and phosphoglycerate kinase 1. Genes encoding the pentose phosphate pathway (PPP) enzymes (transketolase and transaldolase) were upregulated to a similar degree. The expression of genes encoding pyruvate dehydrogenases that block pyruvate flow to the TCA cycle was significantly upregulated. Thus, exposure of PANC1 cells to acute hypoxia resulted in the upregulation of genes that shift the metabolism of cells towards glycolysis and the pentose phosphate pathway (PPP) in adaptation to hypoxic stress.