RNA interference against MDM2 suppresses tumor growth and metastasis in pancreatic carcinoma SW1990HM cells

• Published in: Molecular and cellular biochemistry Vol. 387; no. 1-2; pp. 1 - 8
• Main Authors: Shi, Weidong, Meng, Zhiqiang, Chen, Zhen, Hua, Yongqiang, Gao, Huifeng, Wang, Peng, Lin, Junhua, Zhou, Zhenhua, Luo, Jianmin, Liu, Luming
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-02-2014; Springer; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell growth; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Growth; Humans; Life Sciences; Liver; Liver cancer; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Male; Matrix Metalloproteinase 9 - metabolism; Medical Biochemistry; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Transplantation; Oncology; Pancreatic cancer; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Ribonucleic acid; RNA; RNA Interference; RNA, Small Interfering - genetics; Rodents; Tumor Burden; Tumor proteins; Urokinase-Type Plasminogen Activator - metabolism; MDM2; Cell line; RNA interference; Pancreatic cancer; Liver metastasis
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-011-1208-4

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.