Insulin Promotes Proliferative Vitality And Invasive Capability Of Pancreatic Cancer Cells Via Hypoxia-inducible Factor 1α Pathway

PartⅠThe Study of the Relationship between Insulin and Hypoxia Inducible Factor-1αExpression in Pancreatic CancerObjective: To explore the correlation between the expressions of hypoxia inducible factor-1α(HIF-1α) and insulin levels in pancreatic cancer.Methods: HIF-1αand insulin expression were tested by immunohistochemical method in the center and the edge of pancreatic adenocarcinoma specimen of 65 cases; Meanwhile, Western Blot was used to detect HIF-1αexpression and insulin levels in the center and the edge of pancreatic adenocarcinoma specimen of 28 cases; and analyzed the relationship between HIF-1αexpression and insulin levels.Results: The results of immunohistochemistry and Western Blot showed that HIF-1αprotein expression was both higher in the center and the edge of pancreatic cancers (P>0.05), and insulin level was significantly higher in the edge of specimen than that in the center (P<0.05); HIF-1αprotein and insulin level were positively correlated in the edge of cancerous tissues(r=0.374,P< 0.05), but no significant correlation between them in the center cancerous tissue(r=-0.145,P>0.05).Conclusions: The higher insulin microenvironment in pancreatic cancer may promote the local invasion and metastasis of pancreatic cancer by up-regulating HIF-1α.PartⅡEffects of Insulin on Proliferation and Invasion of Human Pancreatic Cancer CellsObjective: To investigate the effects of insulin on the proliferation and invasion of human pancreatic cancer cells PANC-1, and on HIF-1α, VEGF expression.Methods: PANC-1 was pretreated with insulin of different concentrations. The proliferation of PANC-1 was tested by MTT method, and transwell assay was used to test the invasion ability of PANC-1. HIF-1α,VEGF and PCNA protein expression was assessed by Western blots, and HIF-1α,VEGF mRNA was detected by Real-time PCR.Results: Insulin could increase the proliferation of PANC-1 with the feature of the dose dependency (p<0.05), and PCNA protein expression in the insulin stimulation group was significantly higher than that in the control group (p<0.05). The cells passed through the chamber in insulin pretreated group were much more than matched group (p<0.05), which indicated that the invasive ability of PANC-1 was significantly enforced with insulin stimulation . Insulin could increase the expression of HIF-1α,VEGF protein (p<0.05), and has the maximum stimulating effect in the concentration of 100nM. 100nM insulin stimulating Panc-1 at the time point of 4h could not promote the expression of HIF-1αgene (p>0.05), but could induce VEGF gene expression (p<0.05).Conclusions: High insulin microenvironment could have effect on enhancing the proliferation and invasion of human pancreatic cancer cells, which may be related to the invasion and metastasis of pancreatic cancer.