【摘要】 目的探讨联合转染Survivin和Bcl-2反义寡核苷酸(AsODN)对裸鼠胆囊癌生长抑制作用。方法建立裸鼠胆囊癌皮下移植瘤模型,选择36只裸鼠随机分为3组:对照组、正义寡核苷酸(sODN)组和AsODN组,裸鼠瘤体内分别注射PBS、Survivin和Bcl-2sODN、Survivin和Bcl-2AsODN,12d后处死裸鼠,测量瘤体体积及质量,计算抑瘤率;苏木精-伊红染色观察瘤体组织学变化;免疫组织化学方法检测Survivin及Bcl-2蛋白的表达。结果AsODN组裸鼠瘤体平均体积显著低于对照组、sODN组(F=24.469,q=8.802、7.569,P<0.01),其体积抑瘤率为55.53%,sODN组为9.90%;AsODN组裸鼠瘤体平均质量显著低于对照组、sODN组(F=25.376,q=3.168、20.737,P<0.01),其质量抑瘤率为56.24%,sODN组为8.47%。AsODN组瘤体中可见大量的凋亡细胞。免疫组化证实AsODN组Survivin表达明显降低,同sODN组相比差异有显著意义(F=15.103,q=5.883、7.191,P<0.01);Bcl-2表达亦明显降低,同sODN组相比差异有显著性(F=6.632,q=4.793、4.030,P<0.05)。结论联合转染Survivin和Bcl-2AsODN可下调Survivin和Bcl-2表达,诱发细胞凋亡,从而抑制裸鼠胆囊癌种植瘤的生长。更多还原

【Abstract】 Objective To evaluate the inhibitory action of combining antisense oligonucleotide targeting Survivin and Bcl-2 on growth of gallbladder carcinoma in nude mouse.Methods A model of human gallbladder carcinoma transplanted subcutaneously in nude mice was established.A total of 36 mice were divided into three groups:control group,Survivin and Bcl-2 sODN group,as well as survivin and Bcl-2 AsODN group.Twelve days later,the weight and volume of the tumor were measured and histology observed by HE staining,the expression of survivin and Bcl-2 protein detected by immunohistochemistry SABC method.Results The mean volume and weight of the tumors of AsODN group were significantly lower than that of the controls and sODN group(F=24.469,25.376;q=3.168-20.737;P<0.01).The inhibition rate of volume and weight of AsODN group was 55.53% and 56.24%,respectively,while that of sODN group was 9.90% and 8.47%.A lot of apoptotic cells were seen in tissue sections with HE staining,and the expression of survivin and Bcl-2 protein was markedly lower than that of the control group and sODN group(F=15.103,6.632;q=4.030-7.191;P<0.05).Conclusion Combining antisense oligonucleotide targeting survivin and Bcl-2 could inhibit the growth of subcutaneous tumors in nude mice,the reason might be that they could down-regulate the expression of survivin and Bcl-2 and induce apoptosis of gallbladder carcinoma cell.更多还原