Icariside II suppresses cervical cancer cell migration through JNK modulated matrix metalloproteinase-2/9 inhibition in vitro and in vivo

Abstract

Metastasis contributes a lot to cervical cancer high mortality rate. Icariside II is the principal component of Epimedium brevicornum Maxim and the major functional part to its therapeutic properties. However, the effects and mechanisms of Icariside II on cervical cancer metastasis remain unclear. Using female BALB/c mice with 60 mm3 tumors, we injected mice tail with 25 mg/kg body weight Icariside II or DMSO. After harvesting the tumor, immunohistochemistry and western blot were performed to detect MMP2/9 levels. Icariside II injection significantly inhibited MMP2/9 protein expression. The cell migration assays revealed that Icarisdie II inhibited the wound closure rate and the ability of Hela cell crossing the transwell chambers. Further, the key regulators in NF-κB and MAPK signaling pathway were detected in xenograft tumor and Hela cells by qPCR and western blot. JNK was screened out from several important signaling molecules, which had the same expression trend with MMP2/9. Finally, both 5 μM and 30 μM Icariside II weakened JNK-MMP2/9 signaling, despite the JNK activator Polyphyllin I and Anisomycin reversed the deficiencies. In this study, we proved that Icariside II can inhibit cervical cancer cells migration through JNK-MMP2/9 signaling pathway and is a prospective drug with high-chemopreventive effects on cervical cancer cell metastasis.

Keywords

• Icariside II
• Cell migration
• JNK
• MMP2
• MMP9
• Cervical cancer