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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 investigate the effect of antisense hypoxia inducible factor (HIF) -1α on the growth and metastasis of pancreatic cancer and its relationship with β1-inte-grin. Methods BxPc-3 cells without antisense HIF-1α plasmid were cultured in vitro under hypoxia (0.5% O 2) for 4 h. The hypoxia control group was treated with hypoxia. The antisense HIF -1α plasmid was set as normoxic control group; BxPc-3 cells stably transfected with antisense HIF-1α plasmid under hypoxic conditions (0.5% O 2) for 4h were selected as the experimental group. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of HIF-1α and β1-integrin. Transwell invasive chamber method was used to detect the invasion ability of BxPc-3 cells. After 8 weeks of subcutaneous inoculation of BxPc-3 cells in nude mice, the growth of tumor in each group was observed. Results The expression of HIF-1α and β1-integrin in experimental group was significantly lower than that in control group (P <0.05). The volume, weight and growth rate of tumor in experimental group were much lower than those in control group (P < 0.05). Conclusion Antisense HIF-1α may inhibit the growth and metastasis of pancreatic cancer by blocking the expression of β1-integrin. Therefore, blocking the expression of HIF-1α provides a new way for pancreatic cancer gene therapy.