GANT61 Inhibits Ovarian Cancer SKOV3 Cells Invasion And Migration By Orchestrating CXCL12/CXCR7 Signaling

?Objectives? To detect the expression of GLI1?CXCR4 and CXCR7 in human ovarian cancer tissues and cells and explore the effect of GANT61 on CXCL12/CXCR4/CXCR7 signaling axis in ovarian cancer SKOV3 cells.?Methods? 1.We collected 27 primary ovarian cancer tissues and 13 normal samples from surgically resected tissues from patients in Tongji Hospital.Immunohistochemical technique was used to identify proteins including GLI1,CXCR4 and CXCR7.Meanwhile,the expression levels of these three proteins in ovarian cancer cell lines were detected by western blot.2.Western blot,Quantitative Real-time PCR and immunofluorescence were performed to measure the the expression of GLI1,CXCR4 and CXCR7 and the alteration after treating with GANT61 in ovarian cancer SKOV3 cells.Besides,the change of CXCR4 and CXCR7 expresion levels in ES2 cells after treated by GANT61 was detected by western blot.3.Transwell and scratch test were used for examining the influence of GANT61 on CXCL12-induced invasion and migration in SKOV3 cells.4.Western blot was used for examining the influence of GANT61 on CXCL12-induced phosphorylation of ERK1/2 in SKOV3 cells.?Results? 1.The results of immunohistochemisty demonstrated that GLI1,CXCR4 and CXCR7 were overexpressed in ovarian cancer tissues compared with normal tissues.GLI1 and CXCR7 were mainly distributed in cytoplasm while CXCR4 was more obvious in nucleus.The three proteins were expressed in ovarian cancer cell lines in adifferent degree.2.Compared with control group,after the treatment of GANT61 in SKOV3 cells,the expression of CXCR7 was significantly decreased(P<0.05)while CXCR4 show no statistical difference(P>0.05)in the level of gene and protein.Moreover,the similar result was examined by western blot in ES2 cells.3.GANT61 can inhibit CXCL12-induced invasion and migration in SKOV3 cells.4.GANT61 can block CXCL12-induced phosphorylation of ERK1/2 in SKOV3 cells.?Conclusions? GANT61 can down-regulate the expression of CXCR7 and inhibit ovarian cancer SKOV3 cells invasion and migration by blocking CXCL12-induced phosphorylation of ERK1/2 in SKOV3 cells.