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PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARγ-dependent pathway

机译:PGC-1α通过PPARγ依赖性途径诱导人上皮性卵巢癌细胞凋亡

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Peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 alpha (PGC-1α) coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1α in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1α mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC-1α expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1α in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1α dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PGC-1α-induced apoptosis was partially, but not completely, blocked by PPARγ antagonist (GW9662), and suppression of PPARγ expression by siRNA also inhibited PGC-1α-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1α exerted its effect through a PPARγ-dependent pathway. Our findings indicated that PGC-1α was involved in the apoptotic signal transduction pathways and downregulation of PGC-1α may be a key point in promoting epithelial ovarian cancer growth and progression.
机译:过氧化物酶体增殖物激活受体γ(PPARγ)共激活因子1α(PGC-1α)共激活多种转录因子并调节一些代谢过程。当前的研究调查了PGC-1α在诱导人上皮性卵巢癌细胞凋亡中的作用。通过定量RT-PCR检测人卵巢和人卵巢上皮肿瘤之间的PGC-1αmRNA水平。与正常卵巢相比,在恶性肿瘤的表面上皮中发现较少的PGC-1α表达。 PGC-1α在人上皮性卵巢癌细胞系Ho-8910中的过表达通过Bcl-2和Bax表达的协同调节诱导细胞凋亡。基因芯片分析证实PGC-1α显着影响Ho-8910细胞凋亡相关基因。线粒体功能测定表明,凋亡的诱导是通过细胞色素c释放的终末期进行的。此外,PGC-1α诱导的细胞凋亡被PPARγ拮抗剂(GW9662)部分而非完全阻断,而siRNA抑制PPARγ表达也抑制了PGC-1α诱导的Ho-8910细胞凋亡。这些数据表明PGC-1α通过PPARγ依赖性途径发挥作用。我们的发现表明,PGC-1α参与了凋亡信号转导通路,PGC-1α的下调可能是促进上皮性卵巢癌生长和发展的关键点。

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