人肝细胞癌中转录因子FoxM1表达与甲胎蛋白产生相关

Forkhead box 1 correlates with alpha-fetoprotein production in human hepatocellular carcinoma

摘要:

目的：探讨人肝细胞癌（hepatocellular carcinoma，HCC）中叉头框M1（forkhead box M1，FoxM1）表达与甲胎蛋白（alpha-fetoprotein，AFP）产生的关系。方法：分别采用Western blot和荧光定量PCR（fluorescence quantitative PCR，FQ-PCR）技术检测52例HCC患者肝癌组织中FoxM1蛋白和AFP mRNA表达水平，并查询患者术前血清AFP水平，分析三者相关性；FoxM1特异性抑制剂硫链丝菌素（thiostrepton，TST）和重组FoxM1B腺病毒（adenovirus combined with FoxM1B gene，Ad-FoxM1B）分别作用人HepG2和HepG2.2.15肝癌细胞后，FQ-PCR检测FoxM1 mRNA表达变化，Western blot检测FoxM1蛋白表达变化，电化学发光法检测培养基上清AFP分泌变化。结果：（1）肝癌组织中FoxM1蛋白表达水平与组织中AFP mRNA表达水平及血清AFP分泌水平均呈正相关（r=0.448，P=0.001；r=0.381，P=0.005）；（2）下调FoxM1表达可明显抑制HepG2和HepG2.2.15细胞分泌AFP（P1=0.000，P2=0.000）；（3）FoxM1可明显促进HepG2和HepG2.2.15细胞表达和分泌AFP（P1=0.000，P2=0.000；P1=0.001，P2=0.000）。结论：人肝细胞癌中FoxM1与AFP的表达密切相关，FoxM1可能在促进AFP表达中发挥重要作用。

Abstract:

Objective：To investigate the relationship between forkhead box M1（FoxM1） and alpha-fetoprotein（AFP） in human hepa－tocellular carcinoma（HCC）. Methods：AFP mRNA and FoxM1 protein in 52 HCC tissues were validated by fluorescence quantitative PCR（FQ-PCR） and Western blot. Data of preoperative serum AFP secretion were collected，and the correlation among FoxM1，AFP mRNA and serum AFP were analyzed. HepG2 and HepG2.2.15 cells were treated with thiostrepton（TST） and adenovirus combined with FoxM1B gene. Changes of FoxM1 mRNA and protein were quantified by FQ-PCR and Western blot. AFP in culture supernatant was detected by electrochemiluminescence method. Results：（1）The expression of FoxM1 protein was positively correlated with AFP mRNA and serum AFP（r=0.448，P=0.001；r=0.381，P=0.005）. （2）The decreased expression of FoxM1 could decrease the secretion of AFP in HepG2 and HepG2.2.15 cells（P1=0.000，P2=0.000）. （3）FoxM1 could increase the expression and secretion of AFP in HepG2 and HepG2.2.15 cells（P1=0.000，P2=0.000；P1=0.001，P2=0.000）. Conclusion：FoxM1 protein expression correlates with both in vivo and in vitro AFP production in HCC. FoxM1 possibly play an important role in regulating the expression of AFP.