Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer

作者：Su Feng; Kozak Kathy R; Imaizumi Satoshi; Gao Feng; Amneus Malaika W; Grijalva Victor; Ng Carey; Wagner Alan; Hough Greg; Farias Eisner Gina; Anantharamaiah G M; Van Lenten Brian J; Navab Mohamad; Fogelman Alan M; Reddy Srinivasa T^*; Farias Eisner Robin

来源：Proceedings of the National Academy of Sciences, 2010, 107(46): 19997-20002.

DOI：10.1073/pnas.1009010107

We examined whether reduced levels of Apolipoprotein A-I (apoAI) in ovarian cancer patients are causal in ovarian cancer in a mouse model. Mice expressing a human apoA-I transgene had (i) increased survival (P < 0.0001) and (ii) decreased tumor development (P < 0.01), when compared with littermates, following injection of mouse ovarian epithelial papillary serous adenocarcinoma cells (ID-8 cells). ApoA-I mimetic peptides reduced viability and proliferation of ID8 cells and cis-platinum-resistant human ovarian cancer cells, and decreased ID-8 cell-mediated tumor burden in C57BL/6J mice when administered subcutaneously or orally. Serum levels of lysophosphatidic acid, a well-characterized modulator of tumor cell proliferation, were significantly reduced (>50% compared with control mice, P < 0.05) in mice that received apoA-I mimetic peptides (administered either subcutaneously or orally), suggesting that binding and removal of lysophosphatidic acid is a potential mechanism for the inhibition of tumor development by apoA-I mimetic peptides, which may serve as a previously unexplored class of anticancer agents.

• 出版日期2010-11-16