STAT3反义寡核苷酸对人肺腺癌裸鼠移植瘤生长的抑制作用  

Inhibitory effect of STAT3 antisense oligodeoxynucleotide against human adenocarcinoma of lung derived from A549 cell in nude mice

作　　者：孙顶[1] 蔡建明[1] 祝宝让[1] 程赢[1] 李百龙[1] 崔建国[1] 

机构地区：[1]第二军医大学海军医学系防原医学教研室,上海200433

出　　处：《第二军医大学学报》2011年第1期76-79,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30470415)~~

摘　　要：目的探讨我们自行设计的STAT3(signal transducer and activator of transcription 3)反义核酸(ASODN)对裸鼠肺腺癌A549细胞移植瘤的成瘤能力和移植瘤的抑制作用。方法将经全硫代修饰的STAT3 ASODN加入到培养的A549细胞内,CCK-8法检测细胞生长的抑制率,然后将这种细胞接种于裸鼠颈部皮下,观察肿瘤出现的时间和肿瘤体积的变化,并计算成瘤率。同时取未经处理的A549细胞接种于裸鼠颈部皮下建立移植瘤模型,待瘤结节直径大于5 mm后,分为STAT3ASODN实验组、生理盐水组和无义寡核苷酸对照组。实验组用15 mg/kg ASODN每天1次直接瘤内注射,连续3周,隔日测量肿瘤大小。处理30 d后,剥离瘤块称质量。蛋白质免疫印迹法检测肿瘤中STAT3、p-STAT3的表达。结果 STAT3 ASODN显著抑制A549细胞生长,与无义寡核苷酸组相比,差异有统计学意义(P<0.05)。STAT3 ASODN作用后的A549细胞在裸鼠皮下成瘤能力明显降低,抑瘤率达75.8%。在各组荷瘤动物模型中,生理盐水对照组和无义寡核苷酸对照组的瘤体进行性增大,而STAT3 ASODN处理组的瘤块生长缓慢,与2个对照组相比均有差异(P<0.01),处理30 d后,ASODN处理组的肿瘤质量与2个对照组相比差异均有统计学意义(P<0.05),STAT3 ASODN处理组裸鼠A549细胞移植瘤的生长明显受到抑制,抑瘤率为51.1%。肿瘤中STAT3蛋白表达水平以及磷酸化水平也明显下调。结论 STAT3 ASODN能降低A549细胞的成瘤率、抑制移植瘤生长。Objective To investigate the inhibitory effects of antisense oligodeoxynucleotide（ ASODN） of signal transducer andactivator of transcription 3 （ STAT3） on development and growth of transplanted lung A549 cell adenocarcinoma in nude mice. MethodsThe inhibitory effects of STAT3 ASODN on A549 cell growth was evaluated by CCK-8 assay. STAT3 ASODN-treated A549 cells wereimplanted subcutaneously into nude mice; the tumor growth was observed and the tumor-forming rate was calculated. After subcutaneousimplantation of the untreated A549 cells,the tumor-bearing mice were randomized into 3 groups： control group,STAT3 ASODN group,and nonsense oligodeoxynucleotide （ NSODN） group,with normal saline,STAT3 ASODN,and STAT3 NSODN injected intatumorally （ 15mg/kg daily for 3 weeks） . The tumor volumes were measured every other day and the tumor weights were determined. The proteinexpressions of STAT3 and p-STAT3 in xenografts were examined by Western blotting analysis. Results STAT3 ASODN significantlyinhibited the growth of A549 cells compared with STAT3 NSODN group （ P 0. 05） . The tumor formation ability of A549 cells treated withSTAT3 ASODN was significantly decreased （ with the tumor inhibitory rate being 75. 8% ） . Moreover,the growth of transplanted tumorwas also significantly inhibited in STAT3 ASODN group as compared with those in NSODN group and control group （ P 0. 05） . Thetumor weights were significantly reduced in STAT3 ASODN group than in STAT3 NSODN group and control group （ with the tumorinhibitory rate being 51. 1% ） . The expression of STAT3 protein and p-STAT3 was also down-regulated in STAT3 ASODN group.Conclusion STAT3 ASODN can suppress the tumorigenic ability of A549 cells and inhibit the growth of transplanted tumor in nudemice.

关 键 词：反义寡核苷酸类 STAT3 肺肿瘤 腺癌 肿瘤移植 抑瘤作用 

分 类 号：R734.2[医药卫生—肿瘤]