缺氧诱导因子-1α(HIF-1α)反义寡核苷酸对宫颈癌细胞增殖的影响

The effect of hypoxia inducible factor 1 alpha antisense oligonucleotides on cell proliferation of cervical carcinoma

目的研究缺氧诱导因子-1α反义寡核苷酸(asHIF-1α)对人宫颈癌裸鼠皮下移植瘤的抑制作用及其相关机理。方法使用宫颈癌细胞株He1a建立裸鼠皮下移植瘤模型,将荷瘤裸鼠随机分为3组,分别注射生理盐水,HIF-1α正义寡核苷酸和HIF-1α反义寡核苷酸,观察三组动物的肿瘤生长曲线,四周后处死裸鼠,计算肿瘤的体积及其抑制率,绘制皮下肿瘤生长曲线。应用免疫组化技术检测种植瘤内VEGF和HIF-1α的变化。结果 asHIF-1α有明显的抑瘤作用,肿瘤生长曲线减缓,体积抑制率为33%、瘤重抑制率为54%(P<0.05);反义治疗组种植瘤内HIF-1α和VEGF蛋白含量显著降低(P<0.05)。结论 asHIF-1α对实验动物荷瘤生长具有明显的抑制作用,其机制是通过抑制HIF-1α表达,进而抑制VEGF的合成,从而使肿瘤组织的血管形成被抑制。

Objective To explore the inhibiting effect of hypoxia inducible factor 1 alpha antisense oligonucleotides on the growth of human cervical carcinoma cells in nude mice.Methods Tumors were established by injection of tumor cells named Hela into the shoulder of nude mice.The mice were classified randomly into three groups and treated with saline,antisense oligonucleotide HIF-1α,sense oligonucleotide HIF-1αrespectively.Effects of growth suppression were observed through the volume and the average weight of neoplasia;the expression of HIF-1αand VEGF was examined through immunohistochemical stain.Results The carcinoma cell growth curve was significantly lower after treated with as-HIF-1α.The differences of the average volume and the average weight of neoplasia were statistical significance in group C（treated with as-HIF-1α）（P0.05）.The expression of HIF-1αand VEGF in group C was lowest in all the groups（P0.05）.Conclusion Hpoxia inducible factor 1 alpha antisense oligonucleotides have obviously inhibiting effect on inoculation carcinoma.The mechanism is to inhibit the expression of VEGF through inhibiting HIF-1α.As a result,the formation of tumor vessel was inhibited and the tumor apoptosis was induced.