MDM2 knockdown mediated by a triazine-modified dendrimer in the treatment of non-small cell lung cancer
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Quan Huang1,2,*, Lei Li1,2,*, Lin Li1,*, Hui Chen2, Yongyan Dang2, Jishen Zhang1, Naimin Shao2, Hong Chang2, Zhengjie Zhou2, Chongyi Liu2, Bingwei He2, Haifeng Wei1, Jianru Xiao1
1Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China
2Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China
*These authors have contributed equally to this work
Jianru Xiao, email: email@example.com
Haifeng Wei, email: firstname.lastname@example.org
Keywords: dendrimer, MDM2, gene delivery, siRNA, non-small cell lung cancer
Received: March 22, 2016 Accepted: May 13, 2016 Published: June 01, 2016
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the five-year survival rate is lower in advanced NSCLC patients. Chemotherapy is a widely used strategy in NSCLC treatment, but is usually limited by poor therapeutic efficacy and adverse effects. Therefore, a new therapeutic regimen is needed for NSCLC treatment. Gene therapy is a new strategy in the treatment of NSCLC. However, the lack of efficient and low toxic vectors remains the major obstacle. Here, we developed a biocompatible dendrimer as a non-viral vector for the delivery of mouse double minute2 (MDM2) siRNA in vitro and in vivo to treat NSCLC. The triazine-modified dendrimer efficiently stimulates the down-regulation of MDM2 gene in NSCLC PC9 cells, which induces significant cell apoptosis through the activation of apoptosis markers such as caspase-8 and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the dendrimer/MDM2 siRNA polyplexes showed excellent activity in the inhibition of tumor growth in a PC9 xenograft tumor model. These results suggested that inhibition the expression of MDM2 might be a potential target in NSCLC treatment.
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