Knockdown of MMP12 Inhibits the Growth and Invasion of Lung Adenocarcinoma Cells

Int J Immunopathol Pharmacol. 2015 Mar;28(1):77-84. doi: 10.1177/0394632015572557.

Abstract

Matrix metalloproteinase-12 (MMP12) is involved in many pathological processes including cancer. The expression and function of MMP12 in lung adenocarcinoma (LAC) remain unclear. The present study aimed to investigate the correlation of MMP12 expression with LAC patients and clarify its role in growth and invasion of LAC cells. The expression of MMP12 in human LAC was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was used for observing the effects of lentiviral vector-mediated MMP12 shRNA (shMMP12) on cell growth and invasion in LAC cell lines (A549), indicated by MTT and Transwell assays. We found that the expression of MMP12 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (57.69% vs. 32.69%, P = 0.019), and was closely correlated with the pathological stage and lymph node metastasis of LAC patients (P = 0.01; P = 0.003). Knockdown of MMP12 inhibited proliferation and invasion of LAC cells followed by the downregulation of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). In conclusion, our findings show that high expression of MMP12 is correlated with the pathological stage and tumor metastasis of LAC patients, and knockdown of MMP12 suppresses the development of LAC cells, suggesting that MMP12 may be a promising therapeutic target for the treatment of LAC.

Keywords: MMP12; growth; invasion; lung adenocarcinoma.

MeSH terms

  • A549 Cells
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Matrix Metalloproteinase 12 / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Proliferating Cell Nuclear Antigen / genetics
  • RNA, Small Interfering / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Proliferating Cell Nuclear Antigen
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 12