Abstract
BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease and still continues to have the worst prognosis of all gastrointestinal malignancies. Reports have demonstrated that secretory leukocyte protease inhibitor (SLPI) is overexpressed in various cancers and may be a potential therapeutic strategy for the treatment of different cancers. However, the possible role of SLPI in PDAC is still unknown. In the present study, we investigate the effects of SLPI gene knockdown on the biological behavior of human pancreatic cancer cells. The expressions of SLPI were detected, by qRT-PCR and Western blot, in human PDAC tissues as well as AsPC-1, BxPC-3 and PANC-1 cells. After transfection with siRNA targeting to SLPI, SLPI expression was detected by qRT-PCR and Western blot in cells. Cell proliferation and apoptosis were also evaluated by MTT assay and flow cytometry (FCM). The trans-well assays were also employed to explore the effects of SLPI knockdown on the migration and invasion of PDAC cells in vitro.ResultsThe expressions of SLPI derived from human PDAC and PDAC cell lines were significant higher than those of control groups, respectively (P < 0.05). Regression analysis showed elevated SLPI level was positive correlated with development of PDAC. The siRNA target to SLPI significantly decreased the expressions of SLPI in these PDAC cell lines. Following SLPI-siRNA transduction, the proliferative capacity of the AsPC-1, BxPC-3 and PANC-1 cells was significantly inhibitions, compared to the blank (PDAC-wild type cells) and negative (non-targeting scrambled siRNA transduced PDAC cells) control ones, respectively (P < 0.05). Moreover, SLPI knockdown significantly increased the apoptosis fractions and reduced the migration and invasion of PDAC cells in vitro (P < 0.05).ConclusionsThe present study demonstrated that: i) SLPI played an important role in PDAC progression; ii) SLPI might be an important characteristic of malignant PDAC associated with migration and invasion in vitro; and iii) siRNA targeting to SLPI might be a potential therapeutic strategy for the treatment of PCC.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease and still continues to have the worst prognosis of all gastrointestinal malignancies
secretory leukocyte protease inhibitor (SLPI) expression in PDAC and normal tissues The patients ranged in age from 47 to 69 years, with a median age of 56 years
The current study showed that SLPI elevated in human PDAC tissue and cell lines, including AsPC-1, BxPC-3 and PANC-1 cells
Summary
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease and still continues to have the worst prognosis of all gastrointestinal malignancies. The expressions of SLPI were detected, by qRT-PCR and Western blot, in human PDAC tissues as well as AsPC-1, BxPC-3 and PANC-1 cells. Secretory leukocyte protease inhibitor (SLPI) is present in human mucus secretions and tissues and produced primarily in the epithelial cells lining the respiratory, digestive and reproductive tracts [5,6]. SLPI, 11.7 kDa serine protease inhibitor, is belongs to the whey acidic protein four-disulfide core family of proteins. It binds heparin, a highly sulfated glycosaminoglycan found in mast cell secretary granules, and the interaction increases its effectiveness as an inhibitor of neutrophil elastase [7]. SLPI was reported to play a role in protecting the
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