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

Academic Article

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.
  • Keywords

  • Animals, Apolipoprotein A-I, Cell Line, Tumor, Cell Proliferation, Cell Survival, Disease Models, Animal, Drinking Behavior, Female, Humans, Injections, Lysophospholipids, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neoplasm Transplantation, Ovarian Neoplasms, Peptides, Precancerous Conditions, Survival Analysis, Tumor Burden, Water
  • Digital Object Identifier (doi)

    Authorlist

  • Su F; Kozak KR; Imaizumi S; Gao F; Amneus MW; Grijalva V; Ng C; Wagner A; Hough G; Farias-Eisner G
  • Start Page

  • 19997
  • End Page

  • 20002
  • Volume

  • 107
  • Issue

  • 46