目的

观察缺氧诱导因子1α（HIF-1α）对HepG2细胞增殖相关CyclinD1、CyclinA基因与凋亡相关Survivin、Bcl-2基因的影响。

方法

对Tet-on基因表达系统调控的缺氧诱导因子1α转染入HepG2细胞，用不同质量浓度的强力霉素对受强力霉素调控、稳定表达HIF-1α的HepG2^Tet-on进行凋亡诱导，检测肝癌细胞的凋亡和HIF-1α、CyclinD1、CyclinA、Survivin、Bcl-2的基因表达。

结果

终浓度分别为0、0.1、1、5 mg/L的对HIF HepG2^Tet-on进行细胞凋亡诱导，细胞凋亡率分别为56.4%±7.8%、42.7%±4.9%、31.5%±6.1%、19.7%±4.5%；随着强力霉素浓度的增加，HIF-1α、CyclinD1、CyclinA、Survivin、Bcl-2基因表达水平增加，差异有统计学意义（P ＜0.01）。

结论

HIF-1α基因在体外可以促进HepG2细胞的增殖，抑制其凋亡，而且随着HIF-1α基因表达水平的增加作用不断增强，这可能与HIF-1α诱导CyclinD1、CyclinA、Survivin、Bcl-2基因表达有关。

Objective

To observe the effects of hypoxia-inducible factor 1α (HIF-1α)regulated expression on hepatoma cell proliferation and apoptosis in vitro.

Methods

The Tet-on gene regulated HIF-1α was transfected to HepG2 cell lines and the apoptosis rate,expressions of proliferative protein CyclinD1,CyclinA gene and apoptosis protein Survivin,Bcl-2 gene were detected,HepG2^Tet-on cell apoptosis were induced by different concentrations of doxycycline.

Results

After being incubated under different concentrations of doxycycline for 48 h, HIF-1α gene could increase HepG2^Tet-on cell proliferation and inhibit it's apoptosis, The apoptosis rates were 56.4%±7.8%, 42.7%±4.9%, 31.5%±6.1%, 19.7%±4.5% respectively when the concentraions doxycycine were 0,0.1,1,5 mg/L(P＜0.01).The mRNA expression intensity of HIF-1α,cyclinD1,cyclinA,Survivin,Bcl-2 increased along with the concentration increased of doxycycline (P＜0.01).

Conclusions

HIF-1α gene can increase the proliferation of hepatoma cells and inhibit their apoptosis in vitro in an expression level dependent manner.CyclinD1,CyclinA,Survivin,Bcl-2 expression are involved in the possible mechanism.