Downregulation of GPR4 and TCF7 Promotes Apoptosis and Inhibits Growth and Invasion of Ovarian Cancer Cells.

Abstract

G Protein-coupled Receptor 4 (GPR4) has been reported to play essential roles in regulating the proliferation, migration and angiogenesis of vascular endothelial cells. GPR4 is also suggested to play significant roles in the growth and angiogenesis of ovarian cancer. To explore the functions of GPR4 and Transcription Factor 7 (TCF7) in ovarian cancer. The expression levels of genes involved in Wnt signaling were validated by quantitative Real-Time- PCR (q-RT-PCR). The effects of GPR4 and TCF7 on ovarian cancer cell invasion and apoptosis were determined using soft agar, transwell assay and flow cytometric assay. Protein levels of beta-catenin, MMP-2 and MMP-9 were evaluated by Western blotting. In this study, we found that GPR4 and TCF7 had the capacity to control cell division by altering cell cycle distribution, anchorage-independent growth, and directional cell motility of ovarian cancer cell A2780. Also, we showed that the knockdown of GPR4 and TCF7 in ovarian cancer cell A2780 induced significant inhibitition of cell growth and invasion, as well as the promotion of apoptosis. Downregulation of TCF7 resulted in the decreased MMP-2 and MMP-9 levels. The results implicate that GPR4 behaves like an oncogene and may function through WNT pathway molecule TCF7. Downregulation of GPR4 and TCF7 essentially inhibited cell growth and invasion and enhanced apoptosis of ovarian cancer cells, which may lay a foundation for ovarian cancer treatment.