肝胆肿瘤细胞转录因子Oct-4的表达对Survivin抗凋亡作用的调控

Expression of Oct-4 Transcriptional Factor Rregulates the Anti-Apoptosis Effect of Survivin in Hepatobiliary Cancer Cells

对临床原发性肝癌、胆囊癌、胆管癌标本Oct-4和Survivin的表达进行了免疫组化鉴定;进一步建立肝癌、胆囊癌、胆管癌细胞系EHBH-H1、EH-GB1和EH-CA1,利用腺病毒携带Survivin-shRNA或Oct-4基因感染癌细胞系,并利用流式细胞术观察细胞周期和细胞凋亡的变化,探讨转录因子Oct-4与Survivin之间的相互调控及对癌细胞遗传特性的影响。结果表明,临床原发性肝癌、胆囊癌、胆管癌标本Oct-4阳性率达60.7%,Survivin阳性率达75.0%,且两者之间存在明显的正相关关系;特异性shRNA沉默EH-CA1癌细胞Survivin的表达后,其Oct-4表达没有变化,但诱导细胞周期阻滞和细胞凋亡;EH-GB1癌细胞获得Oct-4表达后,Survivin表达增强,促进细胞周期运行并下调细胞凋亡。实验证实Oct-4可以增强癌细胞Survivin的表达,从而发挥促进细胞周期运行、抑制细胞凋亡的作用,此研究为建立并优化肿瘤基因治疗的策略提供了新的靶点。

The transcriptional factor Oct-4 and Survivin are the key regulatory factors in cancer cell proliferation and mitosis.To investigate the relationship between Oct-4 and Survivin and the effect on genetic characteristics of cancer cells,the expressions of Oct-4 and Survivin were examined immunohistochemically in the clinical specimens of primary hepatocellular carcinoma,gallbladder carcinoma and cholangiocarcinoma.The positive rates of Oct-4 and Survivin were 60.7%and 75.0%,respectively,and there was a parallel relationship between Oct-4 and Survivin in the hepatobiliary cancers.The cancer cell lines of primary hepatocellular carcinoma,gallbladder carcinoma and cholangiocarcinoma,EHBH-H1,EH-GB1 and EH-CA1,were established.The expression of Survivin in EH-CA1 was silenced by adenovirus carrying Survivin-shRNA,and the re-expression of Oct-4 in EH-GBl was done by adenovirus carrying Oct-4 cDNA.The cell cycle and apoptosis were observed by flow cytometry. The results demonstrated that Oct-4 could regulate and enhance the expression of Survivin,then promote the cell cycle progression and inhibit cell apoptosis in cancer cells.This finding provides us a novel target for cancer gene therapy.