Gli1与FoxM1在子宫颈癌组织和细胞中的表达及意义

Significance and Expression of Gli1 and FoxM1 in Cervical Cancer Cells in vitro and in vivo

目的:了解宫颈癌组织和细胞中Gli1及FoxM1的表达及意义,并探究这二者的相关性,进而明确FoxM1是否为Gli1在Hh信号通路中的下游靶基因,从而为宫颈癌的分子靶向治疗提供依据。方法:通过免疫组化链霉素抗生物素蛋白-过氧化物酶(SP)法检测70例宫颈癌组织和10例正常宫颈组织中Gli1及FoxM1的表达;体外培养宫颈癌细胞系Hela、Siha,将两株细胞分别分为5组,分别下调和上调Gli1基因的表达后,应用逆转录(RT)-PCR法检测各组细胞中Gli1及FoxM1的mRNA表达量,并分析二者的相关性。结果:Gli1和FoxM1蛋白表达水平在宫颈癌组织中明显高于正常宫颈组织(P<0.05)。Gli1的表达在分化程度低的宫颈癌组织中较高(P=0.022),与宫颈癌的侵袭程度有关(P=0.005),在有淋巴结转移中更高(P=0.017);FoxM1的表达与宫颈癌的侵袭程度有关(P=0.011),与年龄相关(P=0.033)。Spearman秩相关检验提示,Gli1与FoxM1相关系数r=0.405(P<0.001),呈显著正相关;分别下调Hela细胞和Siha细胞中Gli1表达后,两细胞系中FoxM1mRNA表达量均明显降低,均呈现正显著相关(r=0.613,r=0.729,P<0.05);分别将Gli1过表达质粒导入Hela细胞和Siha细胞中,两细胞系中FoxM1mRNA表达量均明显增高,均呈现正显著相关(r=0.593,r=0.660,P<0.05)。结论:Gli1和FoxM1在宫颈癌组织中均高表达,且Gli1可调控宫颈癌细胞系Hela、Siha中FoxM1的表达,进而促进宫颈癌的发生发展。

Objective：To detect the expression and correlation of Gli1 and FoxM1in cervical cancer cellline Hela and Siha to clarify whether FoxM1 is the target gene of Gli1 in Hh signaling pathways downstream,thus to provide the basis for molecular targeted therapy of cervical cancer.Methods：The expression of Gli1 and FoxM1was detected in 70 cases of cervical cancer tissue and10 cases of normal cervical tissue by immunohistochemical streptavidin peroxidase（SP method）.Cervical cancer cell lines Hela and Siha were cultured and divided into five groups respectively.The mRNA expression of FoxM1 and Gli1in each group was detected by RT-PCR assay after upor down-regulating Gli1 expression and their correlation was also analyzed.Results：The expression of Gli1 and FoxM1in cervical cancer was significantly higher（P〈0.05）than normal cervical tissues.The expression of Gli1 was higher（P=0.022）in the cervical cancer tissues of low differentiation degree,and it was also positively related to the invasive degree of cervical cancer（P=0.005）and lymph node metastasis（P=0.017）.The expression of FoxM1 is associated with the invasion degree of cervical cancer（P=0.011）and age（P=0.033）.Spearman rank suggests Gli1 and FoxM1were significantly positively related as the correlation coefficient was 0.405（P〈0.001）.After down-regulating the expression of Gli1 in Hela and Siha cells respectively,the FoxM1 expression were significantly reduced in both cell lines,showing significant positive correlation（r=0.613,r=0.729,P〈0.05）.After importing over-expression Gli1 plasmid into Siha and Hela cells,the FoxM1 expression were significantly increased,showing significant positive correlation（r=0.593,r=0.660,P〈0.05）.Conclusion：Gli1and FoxM1 are both overexpressed in cervical cancer tissue,and Gli1 can regulate the expression of FoxM1 in cervical cancer cells such Hela and Siha,and then promote the occurrence and development of cervical cancer.