过氧化物酶体增殖物活化受体γ共激活因子1α对人卵巢癌细胞的凋亡作用

目的研究过氧化物酶体增殖物活化受体γ共激活因子1α（PGC-1α）对人卵巢上皮癌细胞凋亡的调控作用。方法选用人卵巢癌细胞株H08910进行体外培养,实验组设3组的对照组加入绿色荧光蛋白（GFP）基因的腺病毒载体,Ad-GFP组（绿色荧光感染）,Ad-PCG-1α组（PCG-1α绿色荧光感染）采用Hoeches染色法检测细胞凋亡,并用流式细胞仪测定凋亡率。定量聚合酶链反应（RT-PCR）检测细胞内凋亡相关基因Bax和Bcl-2mRNA的表达。选用中国仓鼠正常卵巢细胞（CHO）作为对照,同样方法过表达PGC-1仪检测凋亡。结果在人卵巢癌细胞H08910中过表达PGC-1α能明显诱导细胞凋亡,光学显微镜观察到细胞凋亡,流式细胞仪测定凋亡率达58．9％。过表达PGC-1α使H08910细胞内的Bax表达上调1．5倍,而Bcl-2表达下降了69％。而在正常仓鼠卵巢细胞中过表达PGC-1α,细胞未见明显的凋亡发生。结论PGC-1α能显著诱导人卵巢癌细胞发生凋亡,促凋亡基因Bax表达上调和抗凋亡基因Bcl-2表达下降可能是诱发细胞凋亡的机理之一。PGC-1α具有特异性促肿瘤细胞凋亡的作用。

Peroxisome proliferator activated receptor gamma coactivator-1 induces apoptosis in human epithelial ovarian cancer cells

OBJECTIVE: To study the apoptosis-inducing effects of peroxisome proliferator activated receptor gamma (PPARgamma) coactivator-1 (PGC-1alpha) on the human epithelial ovarian cancer cell. METHODS: Human epithelial ovarian cancer cell of the line HO8910 were cultured and divided into 3 groups Ad- PGC-1alpha group (infected with adenovirus. containing PGC-1alpha), Ad- GFP group (infected with adenovirus containing green fluorescent protein, and blank control group. Forty-eight hours later, light microscopy was used to observe the morphological changes of the cells, and apoptosis of the cells was observed by Hoechest staining assay. RT-PCR was used to measure the expression of intracellular Bax and Bcl-2 mRNA. Chinese hamster ovary cells of the line CHO were cultured, infected by adenovirus containing PGC-1alpha and GFP and negative adenovirus respectively, and then underwent Hoechest staining assay and flow cytometry. RESULTS: Light microscopy and Hoechest staining assay showed that there were many morphological characteristics of apoptosis including compaction and margination of nuclear chromatin, nuclear fragments, and apoptotic bodies in the Ad- PGC-1alpha. RT-PCR showed the mRAN expression of intracellular Bax was up-regulated by 1.5 times and the mRNA expression of Bcl-2 was down-regulated by 69% in the Ad- PGC-1alpha group. However, PGC-1alpha treatment did not induce apoptosis in the CHO cells. CONCLUSION: PGC-1alpha induces apoptosis in epithelial ovarian cancer cells in vitro, which may be a result of up-regulation of the pro-apoptotic gene Bax and down-regulation of the anti-apoptotic gene Bcl-2. And over-expression of PGC-1alpha results in no apoptosis in CHO.