title: Combined RNAi targeting human Stat3 and ADAM9 as gene therapy for non-small cell lung cancer.
abstract: 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 determinedin vitroin 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 evaluatedin vivousing A549 xenograft models in nude mice. Thein vitroexperiments 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. Thein vivoexperiments 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.
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Fangchao
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Youbin
authors.initials: Y
authors.lastname: Cui
keywords: RNA silencing; disintegrin and metalloproteinase 9; non-small cell lung cancer; signal transducer and activator of transcription 3