Effects of LPA antagonist and PLD inhibitor on proliferation of human prostate cancer cell lines

Abstract

Lysophosphatidic acid (LPA) is a phospholipid mediator that binds to G protein‐coupled receptors. LPA receptors can activate phospholipase D (PLD), and PLD can participate in LPA production. Previous work from our lab has characterized LPA receptors and response in human prostate cancer cell lines, showing that LPA and EGF can activate PLD and induce LPA production. The current study addresses whether LPA antagonists and/or PLD inhibitors interfere with prostate cancer cell growth. Three human prostate cancer cell lines were used: PC‐3, DU145, and LNCaP. Proliferation assays showed that serum, LPA, and EGF stimulate proliferation of PC‐3 and DU145 cells. Only serum and EGF stimulate proliferation of LNCaP, consistent with published data showing that LNCaP does not respond to LPA. The effects of an LPA receptor antagonist (Ki16425) and a PLD inhibitor (FIPI) were tested. Ki16425 significantly inhibits proliferation of PC‐3 and DU145 in response to LPA and EGF. FIPI inhibits LPA‐ and EGF‐induced growth in PC‐3 and DU145, and also inhibits EGF‐induced proliferation of LNCaP. The observation that an LPA antagonist inhibits EGF response suggests that cross‐talk between EGF and LPA receptors is functionally important. Moreover, the finding that a PLD inhibitor can interfere with proliferation suggests that PLD is a potential therapeutic target in prostate cancer. Supported by an ITHS/INBRE Translational Seed Grant.