TY - JOUR AB - The aim of the present study was to investigate whether interstitial insulin and cancer‑induced hypoxia‑inducible factor-1 (HIF-1) cooperate in pancreatic cancer cells. A population of 45 nude mice were divided into one intact control group and six pancreatic tumor‑carrier groups. Pancreatic tumors were generated using HIF‑1‑positive wild‑type MiaPaCa2 (wt‑MiaPaCa2) pancreatic cancer cells in three groups of carriers and MiaPaCa2 cells transfected with small interfering RNA against HIF‑1α (si‑MiaPaCa2 cells) in the other three carrier groups. To vary the intrapancreatic insulin levels, tumor‑carrying mice were subjected to one of the following conditions: i) Untreated, ii) single injection of the β‑cell toxin streptozotosin prior to cancer cell transplantation and iii) daily injection of insulin following cancer cell transplantation. After 12 weeks, tumor viability was assessed by histological analysis. Western blotting of the tumor grafts was performed to determine the protein expression levels of insulin receptor (IR) and two downstream proteins, hexokinase‑II (HK‑II) and vascular endothelial growth factor (VEGF). Histologically, the greatest viability was observed in wt‑MiaPaCa2 tumors with carriers that remained untreated. These tumors also exhibited greater IR expression than their si‑MiaPaCa2 counterparts, indicating that HIF‑1 is necessary for basal expression of IR. However, IR expression was increased in wt‑MiaPaCa2 and si‑MiaPaCa2 tumors when the carriers were treated with exogenous insulin. This indicates that the insulin‑induced IR expression was independent of HIF‑1. Notably, the insulin‑induced IR expression was associated with increased HK‑II and VEGF expression in wt‑MiaPaCa2 tumors but not si‑MiaPaC2 tumors. Therefore, the present study proposes that insulin and HIF‑1 may cooperate to increase pancreatic cancer cell viability. Furthermore, the HIF‑1 signaling pathway is required for insulin‑induced HK-II and VEGF expression, as well as basal IR expression levels in pancreatic cancer cells. AD - Principal Investigator Unit, Tianjin Institute of Integrative Medicines for Acute Abdominal Diseases, Nankai Hospital, Tianjin 300100, P.R. China Department of Clinical Immunology, Karolinska University Huddinge Hospital, Huddinge SE‑14186, Sweden AU - Zhang,Dapeng AU - Cui,Lihua AU - Li,Shu ,Shun AU - Wang,Feng DA - 2015/09/01 DO - 10.3892/ol.2015.3384 EP - 1550 IS - 3 JO - Oncol Lett KW - pancreatic cancer insulin hypoxia-inducible factor-1α nude mouse PY - 2015 SN - 1792-1074 1792-1082 SP - 1545 ST - Insulin and hypoxia-inducible factor-1 cooperate in pancreatic cancer cells to increase cell viability T2 - Oncology Letters TI - Insulin and hypoxia-inducible factor-1 cooperate in pancreatic cancer cells to increase cell viability UR - https://doi.org/10.3892/ol.2015.3384 VL - 10 ER -