MDM2 knockdown mediated by a triazine-modified dendrimer in the treatment of non-small cell lung cancer.
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.
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.|Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Quan
Q
Huang
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.|Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Lei
L
Li
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
Lin
L
Li
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Hui
H
Chen
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Yongyan
Y
Dang
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
Jishen
J
Zhang
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Naimin
N
Shao
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Hong
H
Chang
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Zhengjie
Z
Zhou
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Chongyi
C
Liu
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, PR China.
Bingwei
B
He
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
Haifeng
H
Wei
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
Jianru
J
Xiao
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D000067492:RNAi Therapeutics / Q000379:methods; D014227:Triazines / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D050091:Dendrimers; D034741:RNA, Small Interfering; D014227:Triazines; D051736:Proto-Oncogene Proteins c-mdm2
MDM2; dendrimer; gene delivery; non-small cell lung cancer; siRNA