The
NAD(+)-dependent deacetylase,
sirtuin 1 (
SIRT1), has been recently been suspected to have a role in
tumorigenesis. We investigated the expression of
SIRT1 in
pancreatic cancer and the effect of SIRT1-targeted RNA interference (RNAi) on cell proliferation and
tumor formation in a
pancreatic cancer cell line, PANC1. The expression of
SIRT1 was investigated in 49 specimens of
pancreatic cancer and adjacent normal pancreatic tissues.
SIRT1 was overexpressed in
pancreatic cancer tissues at both the
mRNA and
protein levels, with increased
SIRT1 positivity associated with
tumors from patients over 60 years old,
tumors larger than 4 cm, higher TNM (extent of
tumor (T), the extent of spread to lymph nodes (N), and presence of distant
metastasis (M)) stage or the presence of lymph node or hepatic
metastases. The PANC-1 was stably transfected with a
SIRT1 small hairpin RNA (
shRNA) expression plasmid and compared with untransfected and PANC-1-negative RNAi cells. Proliferation of PANC-1-SIRT1-RNAi cells was significantly reduced, accompanied by increased rates of apoptosis, G1 arrest and senescence. Furthermore, FOXO3a expression was markedly upregulated in PANC-1-SIRT1-RNAi cells, but no significant difference in p53 expression was observed. The invasive ability of PANC-1-SIRT1-RNAi cells was markedly reduced in vitro, which was linked to increased
E-cadherin and reduced-
MMP expression. Additionally, PANC-1-SIRT1-RNAi cells had a significantly reduced capacity to form
tumors in vivo compared with untransfected and PANC-1-negative RNAi cells. These results suggest that
SIRT1 may promote cell proliferation and
tumor formation in
pancreatic cancer, and downregulation of
SIRT1 using
shRNA could provide a novel therapeutic treatment.