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

  • Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19997-20002. doi: 10.1073/pnas.1009010107.
Feng Su  1 ,  Kathy R Kozak ,  Satoshi Imaizumi ,  Feng Gao ,  Malaika W Amneus ,  Victor Grijalva ,  Carey Ng ,  Alan Wagner ,  Greg Hough ,  Gina Farias-Eisner ,  G M Anantharamaiah ,  Brian J Van Lenten ,  Mohamad Navab ,  Alan M Fogelman ,  Srinivasa T Reddy ,  Robin Farias-Eisner
Affiliations
  • 1. Department of Obstetrics and Gynecology, University of California, Los Angeles, CA 90095-5347, USA.
PMID: 21041624 DOI: 10.1073/pnas.1009010107
Abstract

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.

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