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

2010; National Academy of Sciences; Volume: 107; Issue: 46 Linguagem: Inglês

10.1073/pnas.1009010107

1091-6490

Feng Su, Kathy Kozak, Satoshi Imaizumi, Feng Gao, M. Amneus, Víctor Grijalva, Carey J. Ng, Alan C. Wagner, Greg Hough, Gina Farias-Eisner, G.M. Anantharamaiah, Brian J. Van Lenten, Mohamad Navab, Alan M. Fogelman, Srinivasa T. Reddy, Robin Farias‐Eisner,

Peroxisome Proliferator-Activated Receptors

We examined whether reduced levels of Apolipoprotein A-I (apoA-I) 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.