ORIGINAL ARTICLE

Cell Research (2007): 363-373
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PGC-1α induces apoptosis in human epithelial ovarian cancer cells through a PPARγ-dependent pathway

Yan Zhang^1,*, Yi Ba^2,*, Chang Liu¹, Guoxun Sun¹, Li Ding¹, Songyuan Gao², Jihui Hao², Zhentao Yu², Junfeng Zhang¹, Ke Zen¹, Zhongsheng Tong², Yang Xiang¹ and Chen-Yu Zhang¹

Correspondence: Chen-yu Zhang Tel/Fax: +86-25-83686234; E-mail: cyzhang@nju.edu.cn Yang Xiang, Tel/Fax: +86-25-83685616; E-mail: xiangy@nju.edu.cn Zhongsheng Tong, E-mail: tonghang@medmail.com.cn *These two authors contributed equally to this work

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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.

Cell Research (2007) 17: 363–373. doi: 10.1038/cr.2007.11; published online 20 March 2007

Keywords: PGC-1α, human epithelial ovarian cancer, apoptosis, microarray, PPARγ