SIRT3 is a member of the NAD+-dependent class III deacetylase sirtuin family and plays pivotal roles in regulating cellular functions. Accumulating evidence has recently demonstrated that SIRT3 may function as either oncogene or tumor suppressor in a panel of cancers. However, the biological function of SIRT3 in gastric cancer has been poorly characterized. The present study revealed that the mRNA and protein levels of SIRT3 were significantly reduced in human gastric cancer tissues and cell lines. In addition, overexpression of SIRT3 dramatically suppressed the proliferation ability and colony formation number of gastric cancer cells. By contrast, SIRT3 knockdown using small interfering RNA enhanced tumor cell growth and colony formation. On the molecular level, we found that SIRT3 inhibited the expression of Notch-1 both at the mRNA and protein levels in gastric cancer cells. Furthermore, Notch-1 overexpression diminished the inhibitory effects of SIRT3 on tumor cells proliferation. Taken together, these results demonstrated that SIRT3 suppressed the proliferation gastric cancer cells via down-regulation of Notch-1, which might provide novel therapeutic targets in the gastric cancer therapy.
Keywords: Gastric cancer; Notch-1; SIRT3; cell proliferation.