SIRT 1 Overexpression is Associated with Metastasis of Pancreatic Ductal Adenocarcinoma (PDAC) and Promotes Migration and Growth of PDAC Cells
Siqin Li, Hua Hong, Huicheng Lv, Guozhu Wu, Zhigang Wang
Institute of Ultrasound Imaging, Second Clinical College of Chongqing Medical University, Chongqing, China (mainland)
Med Sci Monit 2016; 22:1593-1600
Available online: 2016-05-12
SIRT 1, as a class III histone deacetylase (HDAC), is implicated in the initiation and progression of malignancies. However, the association of SIRT 1 with tumorigenesis or progression of pancreatic ductal adenocarcinoma (PDAC) is not clear.
MATERIAL AND METHODS: In our study we investigated SIRT 1 expression in PDAC samples and evaluated the association of SIRT 1 level with the clinical and pathological characteristics of PDAC patients. We investigated the role of SIRT 1 in the migration and growth of PDAC PANC-1 or BxPC-3 cells using gain-of-function and loss-of-function approach.
RESULTS: We demonstrated that SIRT 1 mRNA level was significantly promoted in intra-tumor tissues compared to peri-tumor tissues of PDAC; and SIRT 1 overexpression was markedly associated with distant or lymph node (LN) metastasis of these PDAC tissues. Moreover, the in vitro wound healing assay demonstrated that SIRT 1 overexpression with lentivirus vector markedly promoted the migration of PANC-1 or BxPC-3 cells, whereas SIRT 1 knockdown using SIRT 1 specific siRNA transfection significantly inhibited the migration of PDAC cells. The colony forming assay confirmed SIRT 1 promotion of the growth of PANC-1 or BxPC-3 cells.
CONCLUSIONS: In summary, SIRT 1 overexpression is significantly associated with metastasis of PDAC, and overexpressed SIRT 1 plays an important role in pancreatic cancer cell migration and growth. Our data warrants further studies on SIRT 1 as a novel chemotherapeutic target in PDAC.
Keywords: Carcinoma, Pancreatic Ductal - pathology, Cell Line, Tumor, Cell Movement - physiology, Cell Proliferation - genetics, Cell Transformation, Neoplastic - genetics, Disease Progression, Neoplasm Metastasis, Pancreatic Neoplasms - pathology, RNA, Messenger - metabolism, Sirtuin 1 - metabolism