Peptide hormone relaxin produced in normal and cancer prostate cells can stimulate prostate cancer progression. Suppression of relaxin or relaxin receptor RXFP1 expression inhibited prostate cancer both in vitro and in vivo. RXFP1 is a G protein-coupled receptor with the extracellular low density lipoprotein A (LDL-A) module located at the N-terminus. The LDL-A module exhibits a competitive inhibition effect on the RXFP1 function and might be used to suppress relaxin signaling. In this study, we investigated the effect of LDL-A overexpression on prostate cancer cells. PC3 cells expressing the RXFP1-LDL-A module had a decreased proliferation, soft agar colony formation, adhesion, invasion in vitro, and grew at a slower rate than control cells as tumors in xenograft models in mice. Expression analysis revealed that the RXFP1-LDL-A expression in PC3 cells inhibited Akt phosphorylation and MMP2 activation, and led to the down-regulation of several genes previously implicated in tumorigenesis, such as MMP28, S100P, IGFBP2, MUC1 and S100A4. These results indicate that the inhibition of RXFP1 by peptide based on the LDL-A module of this receptor may be a potential approach for prostate cancer suppression.