Targeted inhibition of integrin αVβ3 induces cytotoxicity and suppresses migration ability in ovarian cancer cells and tumor spheroids.

Abstract

Ovarian cancer is a gynecological malignancy that has poor prognosis and high lethality. Integrin αVβ3 is highly expressed in solid cancer cells, including ovarian cancer, and is important in proliferation and cell migration. In this study, we performed two-dimensional (2D) and three‑dimensional (3D) cell culture systems to investigate the potential of integrin αVβ3 as a therapeutic target for ovarian cancer. Inhibition of integrin αVβ3 by antagonist cilengitide (CGT) and shRNA significantly reduce the cell viability of ovarian cancer cells. Co-treatment of CGT and cisplatin induced synergistic cytotoxicity in SKOV3 cells. CGT reduced the protein expressions of phospho-FAK, CD44, and PD-L1. CGT reduced mitochondrial membrane potential and induced apoptotic cell death. To mimic the tumor growth in the extracellular matrix, a tumor spheroid formation assay was performed with Matrigel and epidermal growth factor (EGF). CGT reduced the size of spheroids that grew in 50% Matrigel with or without EGF induction. CGT also enhanced the inhibiting effect of T cells on tumor spheroids. The cell migration ability of SKOV3 cells was blunted by CGT by tumor spheroid-based migration assay. This study used 2D and 3D cell models to provide novel insight into ovarian cancer therapy by targeting integrin αVβ3 and suitable cell models for searching integrin αVβ3-targeting drugs.