【摘要】 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)对肺癌A549细胞裸鼠移植瘤的抑制作用。方法采用肺癌A549细胞株建立裸鼠移植瘤模型,将其分为ASODN组及空白对照组、脂质体转染组、无义寡核苷酸(SODN)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,逆转录-聚合酶链反应(RT-PCR)检测移植瘤c-FLIP mRNA变化,TUNEL检测凋亡指数。结果 ASODN干预后移植瘤生长缓慢,22 d时瘤体积达到最大,此后呈缩小趋势,终末瘤体积及瘤重分别为(376.9±45.8)mm3、(512.4±33.6)mg,明显低于其他各组(P<0.01),抑瘤率为64.31%;ASODN组移植瘤组织增殖指数为(25.71±5.42),c-FLIPmRNA表达量为(0.30±0.05),c-FLIP蛋白表达阳性率为(19.54±6.36),均明显低于各对照组;凋亡指数为(39.68±6.28),明显高于其他各组(P<0.01)。结论 c-FLIP-ASODN对肺癌A549细胞裸鼠移植瘤生长有抑制作用,其机制与降低c-FLIP mRNA和蛋白表达、抑制移植瘤细胞的增殖活性和促进肿瘤细胞凋亡有关。更多还原

【Abstract】 Objective To study the inhibitory effect of cellular Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein(c-FLIP) antisense oligodeoxy nucleotides(ASODN) on transplantation tumor of lung cancer cell line A549 in nude mice.Methods The nude mice bearing A549 cancer cells were applied to detect the effect of c-FLIP-ASODN in vivo.Control group,liposome group,sense oligonucleotide(SODN)group were set for comparison.The growth curve of transplantation tumor was drawn and inhibition ratio was calculated according to tumor weight.Immunohistochemistry was used to examine the expression of c-FLIP and Ki-67 antigen of the transplantation tumor.RT-PCR was used to examine the expression of c-FLIP mRNA.Terminal deoxynucleotidyl transferase mediated uridine triphosphate(UTP) nick end labeling(TUNEL) was used to examine the apoptosis index of the transplantation tumor.Results The transplantation tumor of ASODN group developed slowly after the treatment.The tumor volume and the tumor weight of ASODN group were 512.4±33.6 and 376.9±45.8 mm3 and were smaller than those of the control group with a tumor inhibiting rate of 64.31%.The expression of c-FLIP mRNA and protein,Ki-67 antigen of ASODN group were 0.30±0.05,19.54±6.36,and 25.71±5.42,respectively,lower than those of the control group.The apoptosis index of the transplantation tumor of ASODN group was 39.68±6.28 and higher than that of the control group,with statistically significant difference(P<0.05).Conclusion c-FLIP-ASODN has anticancer activity on lung cancer cell line A549 in vivo.The inhibition in vivo is related to the decreased expression of c-FLIP mRNA and protein and increased apoptosis of the cancer cell.更多还原