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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 expressions of Oct-4 and Survivin in clinical primary hepatocellular carcinoma, gallbladder carcinoma and cholangiocarcinoma specimens were identified by immunohistochemistry. The expressions of EHBH-H1, EH-GB1 and EH-CA1 in hepatocellular carcinoma, gallbladder carcinoma and cholangiocarcinoma were further established, The adenovirus carrying Survivin-shRNA or Oct-4 gene was used to infect the cancer cell lines. The changes of cell cycle and apoptosis were observed by flow cytometry. The mutual regulation of transcription factor Oct-4 and Survivin, The impact of genetic characteristics. The results showed that the positive rate of Oct-4 in clinical primary hepatocellular carcinoma, gallbladder carcinoma and cholangiocarcinoma was 60.7%, the positive rate of Survivin was 75.0%, and there was a significant positive correlation between them. The specific shRNA silence EH-CA1 The expression of Survivin in cancer cells did not change the expression of Oct-4, but induced cell cycle arrest and apoptosis. The expression of Survivin increased after Oct-4 expression in EH-GB1 cancer cells, promoted the cell cycle operation and down-regulated the expression of Death. Experiments confirmed that Oct-4 can enhance the expression of Survivin in cancer cells and thus play a role in promoting cell cycle operation and inhibiting apoptosis. This study provides a new target for the establishment and optimization of strategies for gene therapy of tumors.