RNAi-mediated MMP-9 silencing inhibits mouse melanoma cell invasion and migration in vitro and in vivo

Cell Biol Int. 2013 Aug;37(8):849-54. doi: 10.1002/cbin.10107. Epub 2013 Apr 19.

Abstract

MMP-9 participates in tumour growth, invasion, metastasis and vascularisation. Thus, inhibition of MMP-9 may be involved in the process of tumourigenesis. We have investigated the effect of RNAi-mediated MMP-9 silencing on inhibiting invasion and migration of mouse melanoma cell B16. A specific and optimised siRNA vector was used to target MMP-9 mRNA synthesis in B16 cells. Changes of invasion and migration capability of B16 cell were examined after transfection at different time, and a footpad tumour model was performed to measure the effect of MMP-9 siRNA on melanoma tumourigenesis in vivo. In vitro, down-regulation of MMP-9 expression significantly inhibited B16 cell invasion and migration. In vivo, intratumoural injection of plasmid DNA expressing MMP-9 siRNA every 3 days for three times remarkably inhibited melanoma growth and also suppressed tumour metastasis. The results indicate that RNA-mediated targeting of MMP-9 may have promising applications for the treatment of melanoma.

Keywords: MMP-9; anti-cancer therapy; invasion; melanoma; metastasis; siRNA; tumour growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement*
  • Gene Knockdown Techniques
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma, Experimental / enzymology*
  • Melanoma, Experimental / secondary
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • Tumor Burden

Substances

  • RNA, Small Interfering
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse