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Effects of Jagged1 gene silencing on secretion of vascular-related factors and cell migration in human pancreatic cancer cells SW1990 and PANC1

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Author:
No author available
Journal Title:
Chinese Journal of Pancreatology
Issue:
5
DOI:
10.3760/cma.j.issn.1674-1935.2011.05.005
Key Word:
胰腺肿瘤;Jagged1;血管生成诱导剂;血管内皮生长因子;RNA干扰;Pancreatic neoplasms;Jagged1;Angiogenesis inducing agents;Vascular endothelial growth factor;RNA interference

Abstract: Objective To investigate the effects of Jagged1 gene silencing on the expression of VEGF,angiopoietin 2,bFGF,MMP 9,and the migration of human pancreatic cancer cells SW1990 and PANC1.Methods Jagged1 siRNA and control siRNA were transfected into human pancreatic cancer cells SW1990 and PANC1 respectively.The expressions of Jaggedl mRNA and protein were detected by real-time PCR and Western blotting.ELISA was used to detect the concentration of VEGF,angiopoietin 2,bFGF,MMP9 in cell supernatants.Transwell was used to detect the migration of SW1990 and PANC1 cells.Results Jagged1 mRNA and protein were highly expressed in human pancreatic cancer cells SW1990 and PANC1.After transfected with 15 nmol/L Jagged1 siRNA for 72 h,the expression of Jagged1 mRNA in SW1990 was inhibited and reduced by (59.62 ±2.75)% and in PANC1 reduced by (76.96 ±6.16)% when compared with that in control siRNA group.The Jagged1 protein expression was almost inhibited.The concentration of VEGF in the culture supernatants of SW1990 and PANC1 cells was significantly decreased[( 867.93 ± 58.69 ) pg/ml vs.(1516.24 ±37.58)pg/ml,951.13 ± 120.49)pg/ml vs.(1413.68 ±33.56)pg/ml,P <0.05],but the protein concentration of angiopoietin 2,bFGF,MMP9 were not significantly changed.In addition,after transfected with Jagged1 siRNA,tne expression of VEGF mRNA was (52.26 ± 4.85 )% of the control levels in SW1990 ( P < 0.05),and (59.75 ± 4.91 ) % of the control levels( P < 0.05 ) in PANC1.The number of cell migration of transfected SW1990 and PANC1 was 65.25 ± 5.56 and 57.50 ± 8.58,which were significantly lower than thosein the control siRNA group (122.25±11.09,112.00±12.52,P<0.05).Conclusions Jagged1 is highly expressed in human pancreatic cancer cells.Jagged1 gene silencing significantly inhibits the production and secretion of VEGF in SW1990 and PANC1 cells,and reduces the migration of cancer cells in vitro.

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