1. ¹State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
2. ²Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

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

Received 20 November 2006; Revised 22 January 2007; Accepted 4 February 2007.

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR) coactivator-1 alpha (PGC-1) coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1 in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1 mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC-1 expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1 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-1 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-1-induced apoptosis was partially, but not completely, blocked by PPAR antagonist (GW9662), and suppression of PPAR expression by siRNA also inhibited PGC-1-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1 exerted its effect through a PPAR-dependent pathway. Our findings indicated that PGC-1 was involved in the apoptotic signal transduction pathways and downregulation of PGC-1 may be a key point in promoting epithelial ovarian cancer growth and progression.