RNA interference against MDM2 suppresses tumor growth and metastasis in pancreatic carcinoma SW1990HM cells.
In our previous study, the mouse double minute 2 (MDM2) was identified as one of the leading genes that promote the metastasis of pancreatic cancer (PC). However, the mechanism by which MDM2 promotes metastasis of PC is not understood. In this study, we show that down-regulation of MDM2 through lentivirus-mediated RNA interference could also suppress in vitro proliferation and in vivo tumor growth, and led to an obvious inhibition of both in vitro invasion and in vivo live metastases of SW1990HM cells which had an over-expression of MDM2 and a higher metastatic potential. Moreover, we also show that the down-regulation of MDM2 induced a significant decrease in MMP9, Ki-67 and increase in P53, E-Cadherin expression, and results in an altered expression of genes involved in metastasis, apoptosis, and cell proliferation. Our results suggest that MDM2 plays an important role in metastasis as well as tumor growth of PC. MDM2 could be a hopeful target for the control of PC.
Department of Integrative Oncology, and Department of Oncology, Shanghai Medical College, 270 Dong An Road, Shanghai, 200032, People's Republic of China, swd424@163.com.
Weidong
W
Shi
Zhiqiang
Z
Meng
Zhen
Z
Chen
Yongqiang
Y
Hua
Huifeng
H
Gao
Peng
P
Wang
Junhua
J
Lin
Zhenhua
Z
Zhou
Jianmin
J
Luo
Luming
L
Liu
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D034741:RNA, Small Interfering; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D014568:Urokinase-Type Plasminogen Activator; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9