c-FLIP反义寡核苷酸对食管癌EC109细胞裸鼠移植瘤抑制作用的实验研究

目的研究细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白反义寡核苷酸（c-FLIP-ASODN）对食管癌EC109细胞裸鼠移植瘤的作用。方法采用食管癌EC109细胞株建立裸鼠移植瘤模型，将其分为空白对照组、脂质体转染组、无义寡核苷酸（SODN）组、ASODN组。通过移植瘤生长曲线、终末瘤重，免疫组化法检测c-FLIP蛋白表达、增殖指数，RT-PCR检测移植瘤c-FLIP-mRNA变化，TUNEL检测凋亡指数，观察c-FLIP-ASODN对食管癌裸鼠移植瘤的作用。结果ASODN组治疗后移植瘤生长缓慢，实验结束时ASODN组瘤重及瘤体积明显低于其它各组，抑瘤率为68.19％。ASODN组移植瘤组织c-FLIP-mRNA及蛋白、Ki-67抗原表达较其它各组明显减少，而移植瘤细胞凋亡指数明显高于其它各组(P均<0.01)。其余三组上述指标间比较差异无统计学意义(P>0.05)。结论c-FLIP -ASODN对食管癌EC109细胞裸鼠移植瘤生长有抑制作用，其机制与降低的c-FLIP-mRNA和蛋白表达、抑制移植瘤细胞的增殖活性及促进肿瘤细胞凋亡有关。

Inhibitory effect of c-FLIP-ASODN on transplantation tumors of the esophagus cancer cell line EC109 in nude mice: an experimental study

Objective To 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 the esophagus cancer cell line EC109 in nude mice.Methods 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.A transplantation tumor growth curve was drawn,and the inhibition ratio was calculated according to the tumor weight.The immunohistochemistry SP method was used to determine the expression of c-FLIP and Ki-67 antigen of the transplantation tumors.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 tumors.Results The transplantation tumors 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 tumors 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 the esophagus cancer cell line EC109 in vivo,which is related to its role in decreasing the expressions of c-FLIP mRNA and protein,inhibiting the growth of the transplantation tumors and inducing the apoptosis of cancer cells.