Karyopherina 2 knockdown inhibits osteosarcoma cell proliferation and angiogenesis in mice by suppressing Sox2 expression

Abstract

Objective To explore the effect of karyopherina 2 (KPNA2) knockdown on osteosarcoma cell proliferation and angiogenesis and the possible molecular mechanism. Methods We transfected Saos-2 cells with a Sh-KPNA2 lentiviral vector or a control vector (Sh-Control) to observe the effect of KPNA2 knockdown on the cell proliferation. We further observed tumor angiogenesis in nude mice bearing xenografts derived from Saos-2 cells transfected with Sh-KPNA2 or Sh-Control vector using a fluorescence molecular tomography (FMT) system. qRT-PCR and Western blotting were performed to detect the mRNA and protein expression of KPNA2 and SRY-related HMG box-2 (Sox2) in the xenografts. Results Saos-2 cells transfected with Sh-KPNA2 vector showed significantly lowered proliferation capacity as compared with the cells transfected with Sh-Control vector (P < 0.05). In the tumor-bearing nude mice, the tumor volume and weight were both significantly lower in Sh-KPNA2 group than in Sh-Control group (P < 0.05). The results of FMT scan and immunohistochemistry both showed weakened angiogenesis in the xenografts in Sh-KPNA2 group in comparison with Sh-Control group (P < 0.05). Sox2 expression at both the mRNA and protein levels in the xenografts was significantly lower in Sh-KPNA2 group than in Sh-Control group (P < 0.05). Conclusion KPNA2 knockdown inhibits the proliferation and angiogenesis of osteosarcoma cells possibly as a result of lowered expression of Sox2.

Keywords

• karyopherina 2
• osteosarcoma cell
• cell proliferation
• tumor angiogenesis
• sox2
• nude mice