PMID- 26622706
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 10
IP  - 3
DP  - 2015 Sep
TI  - Insulin and hypoxia-inducible factor-1 cooperate in pancreatic cancer cells to 
      increase cell viability.
PG  - 1545-1550
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-1alpha (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 beta-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.
FAU - Zhang, Dapeng
AU  - Zhang D
AD  - Principal Investigator Unit, Tianjin Institute of Integrative Medicines for Acute 
      Abdominal Diseases, Nankai Hospital, Tianjin 300100, P.R. China.
FAU - Cui, Lihua
AU  - Cui L
AD  - Principal Investigator Unit, Tianjin Institute of Integrative Medicines for Acute 
      Abdominal Diseases, Nankai Hospital, Tianjin 300100, P.R. China.
FAU - Li, Shu Shun
AU  - Li SS
AD  - Department of Clinical Immunology, Karolinska University Huddinge Hospital, 
      Huddinge SE-14186, Sweden.
FAU - Wang, Feng
AU  - Wang F
AD  - Principal Investigator Unit, Tianjin Institute of Integrative Medicines for Acute 
      Abdominal Diseases, Nankai Hospital, Tianjin 300100, P.R. China ; Department of 
      Surgery, Karolinska University Huddinge Hospital, Huddinge SE-14186, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20150617
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4533292
OTO - NOTNLM
OT  - hypoxia-inducible factor-1alpha
OT  - insulin
OT  - nude mouse
OT  - pancreatic cancer
EDAT- 2015/12/02 06:00
MHDA- 2015/12/02 06:01
PMCR- 2015/06/17
CRDT- 2015/12/02 06:00
PHST- 2014/09/19 00:00 [received]
PHST- 2015/05/20 00:00 [accepted]
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2015/12/02 06:01 [medline]
PHST- 2015/06/17 00:00 [pmc-release]
AID - OL-0-0-3384 [pii]
AID - 10.3892/ol.2015.3384 [doi]
PST - ppublish
SO  - Oncol Lett. 2015 Sep;10(3):1545-1550. doi: 10.3892/ol.2015.3384. Epub 2015 Jun 
      17.