TGFbl Receptor Kinase Inhibitor Inhibits Prostate Cancer Growth in Bone

Background and objective Bone metastases （BM） are the primary cause of morbidity and mortality of prostate cancer （PCa） and no effective therapy is currently available. Transforming growth factor （TGF）-β1 has been implicated in the pathophysiology of PCa BM. TGF-β1 is a pleiotropic growth factor that regulates cellular proliferation, chemotaxis, cellular differentiation, immune response, and angiogenesis. TGF-β1 receptors are transmembrane serine/threonine kinases. Upon TGF- β1 binding the type Ⅱ receptor associates with and phosphorylates the type Ⅰ receptor to initiate signaling. In the present work we tested the antitumor efficacy of a selective TGF- β1 receptor kinase inhibitor （LY2109761, Eli Lilly and Co） in preclinical models of PCa BM. For these studies we used two bone derived PCa cell lines, MDA PCa 2b and PC3 cells.