Apolipoprotein A-I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer.
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.
Department of Obstetrics and Gynecology, University of California, Los Angeles, CA 90095-5347, USA.
Feng
F
Su
Kathy R
KR
Kozak
Satoshi
S
Imaizumi
Feng
F
Gao
Malaika W
MW
Amneus
Victor
V
Grijalva
Carey
C
Ng
Alan
A
Wagner
Greg
G
Hough
Gina
G
Farias-Eisner
G M
GM
Anantharamaiah
Brian J
BJ
Van Lenten
Mohamad
M
Navab
Alan M
AM
Fogelman
Srinivasa T
ST
Reddy
Robin
R
Farias-Eisner
D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004327:Drinking Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D007267:Injections; D008246:Lysophospholipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D047368:Tumor Burden; D014867:Water
D016632:Apolipoprotein A-I; D008246:Lysophospholipids; D010455:Peptides; D014867:Water; C032881:lysophosphatidic acid