The effect of HIF-1α on glucose metabolism, growth and apoptosis of pancreatic cancerous cells

Objectives: The aim of this study is to explore the possible role of HIF-1 alpha in glucose metabolism, proliferation and apoptosis of pancreatic cancerous cells. Method: The pancreatic cancerous BxPC-3 cells were cultured in normoxia or hypoxia (3% O-2), respectively. Cell proliferation was determined by MTT assay, apoptosis was determined by Annexin V/PI staining. Expression of Pyruvate dehydrogenase kinase (PDK1), Lactate dehydrogenase (LDHA), pyruvate kinase M2 (PKM2) and citrate synthase (CS) was determined by Western-blot and Real-time PCR. Results: Under hypoxia, the expression of HIF-1 alpha and the lactate production were increased. The expression of glucose metabolic enzymes PDK1, LDHA, PKM2 was also increased compared with that under aerobic condition. Hypoxia treatment had little effect on expression of CS. Under hypoxia, knockdown of HIF-1 alpha inhibited the production of lactate and the expression of PDK1, LDHA and PKM2. Knockdown of HIF-1 alpha repressed the growth of pancreatic cancer BxPC-3 cells and induced apoptosis of the cells under hypoxia. Conclusion: Under hypoxia, the expression of HIF-1 alpha is induced, leading to the increase of glycolysis in BxPC-3 cells possibly through upregulation of the enzymes related to glycolysis. HIF-1 alpha knockdown can inhibit the prolife ratio and promote apoptosis of pancreatic cancerous BxPC-3 cells in vitro.