RNA干扰HIF-1α增强宫颈癌BALB/c小鼠移植瘤放射敏感性  

Interference of HIF-1α by RNA to enhance radio sensitivity of HeLa cell tumor transplanted in BALB/c mice

作　　者：袁响林[1] 于世英[1] 庄亮[1] 谢涛[1] 杨彬[1] 董兰兰[1] 熊华[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肿瘤内科,湖北武汉430030

出　　处：《中国癌症杂志》2007年第4期303-306,共4页China Oncology

基　　金：湖北省卫生厅重点资助项目(No:JX1A06)。

摘　　要：背景与目的:缺氧诱导因子-1α(HIF-1α)是一种重要的缺氧应答调控因子,在维持细胞能量代谢、肿瘤血管生成及转移、细胞增殖与凋亡等诸多方面起着重要作用。在子宫内膜癌、卵巢癌,食道癌等肿瘤中,国内外有大量研究报道,但均未有关于HIF-1α与宫颈癌移植瘤放疗敏感性关系的报道。本研究探讨RNA干扰乏氧诱导因子-1α增强宫颈癌BALB/c小鼠移植瘤放射敏感性的作用。方法:构建干扰HIF-1α质粒HIF-1α-shRNA,采用Westernblot方法观察有氧与乏氧状态下RNA干扰HIF-1α蛋白的变化。将20只裸鼠分随机为两组,其中对照组接种含pGenesil-1空白质粒人宫颈癌HeLa细胞(命名为H0),实验组接种含HIF-1α-shRNA质粒的HeLa细胞(命名为H1),待裸小鼠右后大腿外侧皮下移植瘤长至直径8.0mm时,在两组中各取5只进行照射,计算两组裸鼠移植瘤长至14.0mm时的生长延缓时间。结果:①Westernblot分析乏氧状态下对照组检测到HIF-1α蛋白质条带,常氧状态下实验组和对照组及乏氧状态下的实验组均未检测到HIF-1α蛋白质表达。②两组移植瘤从8.0mm生长到14.0mm时生长延缓时间分别为8d及14d(P<0.05)。结论:RNA干扰HIF-1α可增强BALB/c小鼠宫颈癌移植瘤的放射敏感性。Background and purpose： Hypoxia inducible factor-1α/HIF-1α） is an important regulator because HIF- 1α can bind to special situs of hypoxia response gene when cells response to hypoxie environment. It plays a crucial roles in cell energy metabolisms, tumor angiogeuesis and metastasis, cell proliferation and apoptosis. There were a lots of reports about the implication of HIF-1α in endometrial cancer, ovarian cancer, esophageal cancer and so on. But the role of HIF-1α in the radiosensitivity of cervical transplanted tumors. This study was to investigate the impacts of silenced HIF-1α through RNA interference in the radiosensitivity of xenograft of HeLa cell. Methods： HIF-1α RNA interference vector（ pGenesil- HIF-1α-shRNA） was constructed and the expression of HIF-1α in HeLa cells line treated by RNA-interference was analyzed under both normoxia and hypoxia condition by Western blot. 20 nude mice were divided into two groups. The control group was inoculated with pGenesil-1 plasmid transfeeted HeLa line（ named H0）, and the experimental group with HIF-1α- shRNA plasmid （ named H1 ）. When the largest diameter of each transplantation tumor in the right back thigh of the nude mice reached 8.0 mm, 5 nude mice from both groups were radiated, then the period of tumor growth from 8.0 mm to 14. 0 mm was recorded. Results： ①By the means of Western blot, there was a HIF-1α strap under hypoxia state in the control group; but no HIF-1α strap could be found either under normoxia in experimental/control group, or under hypoxia in experimental group. ②The period of tumor growth from 8.0 mm to 14.0 mm was eight days in the control group, and 14 days in experimental group （P 〈 0.05）. Conclusions： Silencing of HIF-1α through RNA-interference can increase the radiosensitivity of transplanted cervical cancer in nude mice.

关 键 词：宫颈癌 乏氧 移植瘤 放射敏感性 

分 类 号：R73-362[医药卫生—肿瘤]