Combined RNAi targeting human Stat3 and ADAM9 as gene therapy for non-small cell lung cancer.

Previous studies have demonstrated that human signal transducer and activator of transcription 3 (Stat3) and disintegrin and metalloproteinase 9 (ADAM9) are promising targets for RNA interference (RNAi)-based gene therapy for human non-small cell lung cancer (NSCLC). Thus, in the present study, the recombinant lentiviral (Lv) small hairpin (sh)RNA expression plasmids Lv/sh-Stat3 and Lv/sh-ADAM9, which targeted Stat3 and ADAM9, respectively, were constructed and subsequently infected into the A549 human NSCLC cell line. Cell proliferation, migration, invasion and apoptosis were determined in vitro in A549 cells following treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone or in combination. In addition, the combined effect of Lv/sh-Stat3 and Lv/sh-ADAM9 gene therapy was evaluated in vivo using A549 xenograft models in nude mice. The in vitro experiments demonstrated that A549 cells treated with a combination of Lv/sh-Stat3 and Lv/sh-ADAM9 exhibited a significant additive effect in their cell proliferation, migration, invasion and apoptosis abilities, compared with A549 cells treated with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. The in vivo experiments conducted in A549 xenograft tumor mouse models revealed that the combined treatment with Lv/sh-Stat3 and Lv/sh-ADAM9 exerted an additive effect on tumor growth inhibition, compared with the treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. These results suggested that combined RNAi gene therapy targeting human Stat3 and ADAM9 may be a novel and promising strategy for the treatment of NSCLC.