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作 者:刘涛[1] 王统玲[1] 勾善淼[1] 殷涛[1] 汪理[1] 周伟[1] 李永峰[1] 王春友[1]
机构地区:[1]华中科技大学同济医学院附属协和医院胰腺外科,湖北武汉430022
出 处:《中华胰腺病杂志》2012年第1期19-21,共3页Chinese Journal of Pancreatology
基 金:国家自然科学基金(30801098)
摘 要:目的研究胰岛素对人胰腺癌PANC1细胞增殖、侵袭能力及细胞低氧诱导因子(HIF.1d)、血管内皮生长因子(VEGF)表达的影响。方法采用0.1、1、10、100nmol/L胰岛素处理PANC1。噻唑蓝法和Transwell小室侵袭实验检测细胞增殖和侵袭能力;蛋白质印迹法和实时PCR法检测增殖性细胞核抗原(PCNA)及HIF—1α、VEGF蛋白和mRNA的表达。结果胰岛素呈剂量依赖性诱导PANC1细胞的增殖,上调HIF-1α、VEGF蛋白表达。100nmol/L胰岛素干预4d,PANC1细胞的PCNA蛋白表达显著上调(1.196±0.014比1.157±0.013,P〈0.05);Transwell小室穿膜细胞数量显著增加[(141.0±2.1)个比(89.0±1.4)个,P〈0.05];HIF—1α蛋白表达显著上调(1.139±0.020比0.598-t-O.013,P〈0.05),但HIF-1α mRNA表达无明显变化;VEGF蛋白表达显著上调(1.011±O.023比0.6274-0.013,P〉0.05),VEGFmRNA表达亦显著上调(0.970±0.016比0.350±0.013,P〈0.05)。结论高胰岛素微环境可诱导PANC1细胞增殖,并通过上调HIF-1α及VEGF的表达增强细胞的侵袭能力。Objective To investigate the effects of insulin on the proliferation and invasion of human pancreatic cancer cells PANC1, and on its HIF-1α, VEGF expression. Methods PANC1 was pretreated with insulin of different concentrations (0.1, 1, 10, 100 nmol/L). The proliferation of PANC1 was tested by MTT method, and transwell assay was used to test the invasion ability of PANC1. 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 PANC1 in a dose-dependent manner (p 〈 0.05 ), and increase the expression of HIF-1α, VEGF protein. After 100 nmol/L insulin treatment for 4 d, the PCNA protein expression in the insulin group was significantly higher than that in the control group ( 1. 196± 0. 014 vs 1. 157 ± 0. 013, P 〈 0.05). The cancer cells passed through the chamber in insulin group were much more than that in the control group ( 141.0 ±2.1 vs 89.0 ± 1.4, P 〈0.05 ). The expression of HIF-1α protein was significantly increased ( 1. 139 ± 0. 020 vs 0. 598 ±0. 013, P 〈0.05 ), while there was no significant change of HIF-1α mRNA expression. Both the expression of VEGF protein and mRNA were significantly increased ( 1.011 ±0. 023 vs O. 627 ± 0. 013 0. 970 ± 0. 016 vs 0. 350 + 0. 013, P 〈 0. 05 ). Conclusions High insulin microenvironment could enhance the proliferation and invasion of PANC1 cells by up-regulating the expression of HIF-1α and VEGF.
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