Combination of AAV-mediated NUPR1 knockdown and trifluoperazine induces premature senescence in human lung adenocarcinoma A549 cells in nude mice

Nuclear protein 1 (NUPR1)/p8, a transcriptional regulator, has the ability to facilitate lung cancer cell survival. Adeno-associated virus (AAV)-based vectors are efficient vehicles for gene transfer and expression. In this study, an AAV-mediated NUPR1 shRNA vector was constructed that effectively inhibited the expression of NUPR1 in a tumor xenograft model derived from lung adenocarcinoma A549 cells. Trifluoperazine (TFP), which is an antipsychotic drug, has the ability to bind to NUPR1 and mimic NUPR1 deficiency in cancer cells. It was also found that the combination of TFP and AAV-mediated NUPR1 shRNA delivery led to significant tumor growth inhibition in nude mice bearing human lung cancer xenografts. Moreover, AAV-mediated NUPR1 shRNA therapy induced premature senescence in vitro and in vivo. Collectively, the findings of this study suggest a putative role for the combination of AAV-NUPR1 shRNA and TFP in lung cancer therapy.