Targeting β-catenin affects cell survival and tumor growth in an in vitro and in vivo models of ovarian cancer.

MELANIE OCHENDROWITSCH; MARTA TESONE; IRUSTA GRISELDA; SEBASTIÁN BOCCHICCHIO

Helsinski

Congreso; International Meeting of Vascular Biology; 2018

Wnt/β-catenin is a highly conserved pathway that regulates a diversity of cell processes. We studied the effect of Wnt/β-catenin inhibition in human ovarian cancer cell lines and tumor growth. In vitro we analyzed proliferation and migration of IGROV-1 and SKOV-3 cells incubated with the Wnt inhibitors: ICG-001 or XAV939 ( 1, 10, 20, 50 µM). For in vivo studies, IGROV-1 cells were subcutaneously injected in 6-8 weeks-old female nude mice. The Wnt inhibitors XAV939 (2.5 and 5 mg/kg) or ICG-001 (5 and 10 mg/kg) were endovenously administered every two days three times. Mice were euthanized 3 days after the last injection. The incubation with XAV939 or ICG-001 caused a significant decrease in cell proliferation. XAV939 reduced β-catenin levels and one of its target genes, Cyclin D1. Additionally, we observed a significant decrease in cell migration with ICG-001 20 µM, while no changes were detected with XAV939 20 µM. Tumors treated with XAV939 or ICG-001 showed a significant decrease in tumor size in accordance with lower levels of Ki67 and PCNA protein levels. XAV939 reduced tumor β-catenin levels and Cyclin D1. In XAV939-treated animals, there was a decrease in tumor endothelial cell area and hipoxia showed by CD31 and HIF1 α expression. Also, the inhibition of Wnt/β-catenin signaling decreased α-Actin and Angiopoietin 1/2 ratio evidencing a decrease in vessel stability.Conclusion1. Wnt/β-catenin signaling regulates ovarian cancer cell lines proliferation and migration.2. Wnt/β-catenin signaling is involved in ovarian tumor growth.3. Wnt/β-catenin controls ovarian tumor angiogenesis.