| 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,CCK8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STAT3 ASODN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、pSTAT3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。 |
| 关键词: 反义寡核苷酸类 STAT3 肺肿瘤 腺癌 肿瘤移植 抑瘤作用 |
| DOI：10.3724/SP.J.1008.2011.076 |
| 投稿时间：2010-03-30修订日期：2010-12-22 |
| 基金项目:国家自然科学基金(30470415). |
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| Inhibitory effect of STAT3 antisense oligodeoxynucleotide against human adenocarcinoma of lung derived from A549 cell in nude mice |
| SUN Ding,CAI Jian-ming*,ZHU Bao-rang,CHENG Ying,LI Bai-long,CUI Jian-guo |
| (Department of Atomic Irradiation Prevention, Faculty of Navy Medicine, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| ObjectiveTo investigate the inhibitory effects of antisense oligodeoxynucleotide(ASODN) of signal transducer and activator 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 CCK8 assay. STAT3 ASODNtreated A549 cells were implanted subcutaneously into nude mice; the tumor growth was observed and the tumorforming rate was calculated. After subcutaneous implantation of the untreated A549 cells, the tumorbearing 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 (15 mg/kg daily for 3 weeks). The tumor volumes were measured every other day and the tumor weights were determined. The protein expressions of STAT3 and pSTAT3 in xenografts were examined by Western blotting analysis. ResultsSTAT3 ASODN significantly inhibited the growth of A549 cells compared with STAT3 NSODN group (P<0.05). The tumor formation ability of A549 cells treated with STAT3 ASODN was significantly decreased (with the tumor inhibitory rate being 75.8%). Moreover, the growth of transplanted tumor was also significantly inhibited in STAT3 ASODN group as compared with those in NSODN group and control group (P<0.05) . The tumor weights were significantly reduced in STAT3 ASODN group than in STAT3 NSODN group and control group (with the tumor inhibitory rate being 51.1%). The expression of STAT3 protein and pSTAT3 was also downregulated in STAT3 ASODN group. ConclusionSTAT3 ASODN can suppress the tumorigenic ability of A549 cells and inhibit the growth of transplanted tumor in nude mice. |
| Key words: antisense oligonucleotides STAT3 lung neoplasms adenocarcinoma neoplasm transplantation antitumor effect |
