反义缺氧诱导因子-1α对胰腺癌生长转移的影响  

Effect of antisense hypoxia inducible factor-lαon progression and metastasis of pancreatic cancer

作　　者：常青[1] 秦仁义[1] 黄涛[1] 高军[1] 冯延平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院普外科,武汉430030

出　　处：《中华实验外科杂志》2006年第7期837-839,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察反义缺氧诱导因子(HIF)-1α对胰腺癌生长、转移的影响及其与β1-inte- grin的关系。方法缺氧条件下(0．5%O_2)体外培养4h,未转染反义HIF-1α质粒的BxPc-3细胞设为缺氧对照组；常氧条件下体外培养,未转染反义HIF-1α质粒的BxPc-3细胞设为常氧对照组；缺氧条件下(0．5%O_2)体外培养4h,稳定转染反义HIF-1α质粒的BxPc-3细胞设为实验组。采用逆转录-聚合酶链反应(RT-PCR)和Western blot检测HIF-1α和β1-integrin的表达情况。Transwell侵袭室方法检测BxPc-3细胞侵袭能力。裸鼠皮下接种BxPc-3细胞8周后,观察各组肿瘤生长情况。结果实验组HIF-1α和β1-integrin的表达明显降低,迁移的细胞数远少于对照组(P＜0．05)；实验组肿瘤的体积、重量、生长速度远低于对照组(P＜0．05)。结论反义HIF-1α可能通过阻断β1-integrin的表达而抑制胰腺癌的生长和转移。因此,阻断HIF-1α的表达为胰腺癌基因治疗提供了新途径。Objective To observe whether antisense hypoxia inducible factor-1α （HIF-1α） induces the down-regulation of β1-integrin in BxPc-3 cells and the effect on progression and metastasis of pancreatic cancer. Methods BxPc-3 cells not transfected with antisense HIF-1α plasmid and exposed to 0.5 % O2 for 4 h served as hypoxia control group, normoxic BxPc-3 cells not transfected with antisense HIF-1α plasmid as normoxia control group, and the BxPc-3 cells transfected with antisense HIF-1α plasmid and exposed to 0.5 % O2 for 4 h as experimental group. The expression of HIF-1α and β1-integrin was detected by RT-PCR and Western blotting. The migration of BxPc-3 cells was assayed using transwell cell culture chambers. Subcutaneous transplantation of BxPc-3 cells in nude mice for 8 week was performed to assess progression and metastasis of pancreatic cancer, Results The expression levels of HIF-laand β1-integrin were markedly down-regulated in experimental group （P〈0.05 ）. The number of migrated BxPc-3 cells in experimental group was far less than in control group （P〈0.05 ）. In vivo, the tumor size and weight in experimental group were significantly less than those in control group （P〈0.05）. Conclusion Antisense HIF-1αinhibits the expression of β1-integrin and restrains the progression and metastasis of pancreatic cancer. HIF-1α may play a very important role in progression and metastasis of pancreatic cancer. Blocking HIF-1α in pancreatic cancer cells may offer an avenue for gene therapy.

关 键 词：胰腺癌 转移 缺氧诱导因子-1 寡核苷酸类.反义 

分 类 号：R735.9[医药卫生—肿瘤]