喉鳞状细胞癌中PI3K抑制剂对HMGA1基因表达的影响

Effect of PI3K Inhibitor on HMGA1 Gene Expression in Laryngeal Squamous Cell Carcinoma

目的检测磷脂酰肌醇3激酶(PI3K)、高迁移率族蛋白A1(HMGA1)基因在喉鳞状细胞癌(LSCC)中表达情况,观察喉癌Hep2细胞中应用PI3K抑制后HMGA1表达变化,分析LSCC中HMGA1表达在多个临床病理参数组别中的影响。方法采用免疫组化SP法检测47例LSCC组织和21例癌旁正常组织中PI3K和HMGA1基因蛋白水平表达情况,逆转录-多聚酶链反应(RT-PCR)检测PI3K抑制剂(wortmannin)预处理与未处理组的人喉癌Hep2细胞中HMGA1基因mRNA水平表达量,分析LSCC中HMGA1基因表达与各临床病理参数的关系。结果PI3K和HMGA1基因在LSCC中蛋白水平阳性表达率均高于癌旁正常组织,PI3K为(P<0.01),HMGA1为(P<0.05),未加PI3K抑制剂组的人喉癌Hep2细胞中HMGA1 mRNA表达量明显高于预处理组(P<0.01)。LSCC中HMGA1基因蛋白水平表达与临床分期、淋巴结转移、吸烟均相关,与病理分级、年龄、解剖分区均无关。结论喉鳞状细胞癌中PI3K、HMGA1基因在蛋白水平表达均增高,人喉癌Hep2细胞中应用PI3K抑制后明显降低HMGA1基因的表达活性。两基因之间可能关联表达促进喉癌的发生与发展。

Objective To investigate the expression of PI3K(phosphoinostitide 3-kinase)and HMGA1(high mobility group protein A1)in laryngeal squamous carcinoma cell(LSCC).Observe the expression of HMGA1 after PI3K inhibition applicated.Analysis the relationship between expression of HMGA1 and clinical pathological parameter in LSCC.Methods The expression of protein came from PI3K and HMGA1 in 47 LSCC tissues and 21 normal adjacent tissues were determined by SP immunohistochemistry.The expression of HMGA1 mRNA in laryngeal carcinoma Hep2 cells were pretreated by PI3K inhibitor(wortmannin)and untreated groups were detected by reverse transcription-polymerase chain reaction(RT-PCR).The relation between expression of HMGA1 and clinical pathological parameter in tumor tissues was analyzed.Results The positive rate of PI3K(P<0.01)and HMGA1(P<0.05)about proteic expression in LSCC were both higher than those in normal adjacent tissues.The expression of HMGA1 mRNA in group of laryngeal carcinoma Hep2 cells without PI3K inhibitor were higher than those in pretreated group(P<0.01).The proteic expression of HMGA1 in LSCC were associated with clinical stage,lymph node metastasis and smoking,but weren’t associated with pathological grading,age and anatomic site.Conclusion The expression of protein of PI3K and HMGA1 in LSCC are increased,After applied of PI3K inhibitor,the expression of HMGA1 was significantly reduced in laryngeal carcinoma Hep2 cells.The two genes may activate with each other to promote the development and progression in LSCC.