关键词: 裸鼠 , 基因, c-FLIP, 细胞凋亡, 寡脱氧核苷酸类, 反义, 食管肿瘤

Abstract: ObjectiveTo explore the inhibitory effect of cellular Fas-associated death domainlike IL-1 beta converting enzyme inhibitory protein (c-FLIP) antisense oligodeoxynucleotides (ASODN) on transplantation tumor of esophagus cancer cell line EC109 in nude mice. MethodsThe nude mice bearing EC109 cancer cells were established and divided into the control group, the liposome group, the sense oligonucleotide(SODN)group and the ASODN group．The transplantation tumor growth curve was drawn, and the inhibition ratio was calculated according to the tumor weight. Immunohistochemistry SP method was used to determine the expression of c-FLIP and Ki-67 antigen of the transplantation tumor. RTPCR was used to determine the expression of c-FLIP-mRNA. Terminal deoxynucleotidyl transferase mediated UTP nick end labeling (TUNEL) was used to determine the apoptosis of the transplantation tumor. ResultsThe transplantation tumor of the ASODN group slowly grew after taking drugs. The tumor volume and the tumor weight of the ASODN group were decreased compared with those of the other control groups. The tumor inhibitory rate was 68.19％. The expressions of c-FLIP mRNA and protein，and the Ki-67 antigen of the ASODN group were lower than those of other control groups. The apoptosis of the transplantation tumor of the ASODN group was higher than that of the other control groups. There were statistically significant differences between the ASODN group and the other groups(P<0.05), but no statistically significant differences were found among the control group, the liposome group and the SODN group(P>0.05). Conclusion c-FLIP ASODN has an anticancer activity on esophagus cancer cell line EC109 in vivo, which is related to its role in decreasing of the expressions of c-FLIP mRNA and protein, inhibiting the growth of the transplantation tumor and inducing the apoptosis of cancer cells.

Key words: Esophagus cancer, Antisense oligodeoxynucleotides, Apoptosis, Gene therapy, c-FLIP, Nude mice