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目的研究干细胞因子(SCF)和缺氧诱导因子1α(HIF-1α)在胰腺癌中表达的相关性,并探讨SCF对HIF-1α表达的调控机制。方法使用免疫组织化学染色检测胰腺癌标本SCF和HIF-1α的表达,分析两种分子表达的相关性。用(0、1、10、100)ng/m L SCF和5μmol/L c-KIT抑制剂格列卫(Gleevec)单独或联合处理胰腺癌PANC-1细胞,实时荧光定量PCR检测HIF-1αmRNA水平,Western blot法检测HIF-1α蛋白水平、胞外信号调节激酶1/2(ERK1/2)、AKT磷酸化水平。结果胰腺癌组织SCF和HIF-1α的表达上调,二者表达呈正相关。在PANC-1细胞中,SCF不能影响HIF-1α的mRNA表达,但能够上调HIF-1α的蛋白表达,且呈浓度依赖性。Gleevec不能影响HIF-1α的mRNA表达,但能够抑制SCF对HIF-1α蛋白的上调作用,下调ERK1/2、AKT的磷酸化水平。结论 SCF/c-KIT可激活胰腺癌PANC-1细胞AKT和ERK信号通路上调HIF-1α蛋白表达。
Objective To study the correlation between the expression of stem cell factor (SCF) and hypoxia inducible factor 1α (HIF-1α) in pancreatic cancer and to explore the mechanism of SCF regulating the expression of HIF-1α. Methods The expression of SCF and HIF-1α in pancreatic cancer specimens was detected by immunohistochemical staining and the correlation between the expression of two molecules was analyzed. Pancreatic cancer PANC-1 cells were treated with (0, 1, 10, 100) ng / m L SCF and 5 μmol / L c-KIT inhibitor Gleevec separately or in combination and real-time fluorescence quantitative PCR was used to detect HIF- The protein level of HIF-1α, ERK1 / 2 and AKT phosphorylation were detected by Western blot. Results The expressions of SCF and HIF-1α in pancreatic cancer tissues were up-regulated, and the expressions of them were positively correlated. In PANC-1 cells, SCF could not affect the mRNA expression of HIF-1α, but could up-regulate the protein expression of HIF-1α in a concentration-dependent manner. Gleevec can not affect the mRNA expression of HIF-1α, but it can inhibit the upregulation of HIF-1αprotein by SCF and downregulate the phosphorylation of ERK1 / 2 and AKT. Conclusion SCF / c-KIT can activate AKT and ERK signaling pathways in pancreatic cancer PANC-1 cells to up-regulate the expression of HIF-1α.