RNAi-mediated A disintegrin and metalloproteinase 9 gene silencing inhibits the tumor growth of non-small lung cancer in vitro and in vivo.

Abstract

A disintegrin and metalloproteinase 9 (ADAM9) is a type I transmembrane protein that has been associated with cancer development and metastasis in various types of cancer. However, little is known about its role in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether downregulation of ADAM9 affects cell proliferation, apoptosis, migration and invasion in NSCLC. Thus, a recombinant lentiviral small hairpin RNA expression vector carrying ADAM9 was constructed and infected into the human NSCLC cell line A549. Cell proliferation, apoptosis, migration and invasion in vitro and tumor growth in vivo were determined following downregulation of ADAM9 by RNA interference-mediated ADAM9 gene silencing. It was found that downregulation of ADAM9 expression using an RNA silencing approach in A549 tumor cells significantly inhibited cell proliferation, migration and invasion, induced cell apoptosis in vitro, as well as suppressed in vivo tumor growth in an experimental mouse model of lung metastasis. These data indicate that ADAM9 is potentially an important new therapeutic target for the prevention of tumor growth in NSCLC.