The Histone Deacetylase SIRT6 Inhibits Ovarian Cancer Cell Proliferation via Down-Regulation of Notch 3 Expression

Eur Rev Med Pharmacol Sci. 2015;19(5):818-24.

Abstract

Objective: SIRT6 belongs to the NAD+-dependent class III deacetylase sirtuin family. Accumulating evidences have supported the critical role of SIRT6 in the proliferation, differentiation, cell cycle progression and apoptosis of cancer cells. The present study aims to determine the expression of SIRT6 in human ovarian cancer tissues and further investigate its the biological effect in ovarian cancer.

Materials and methods: Real time PCR and western blot were performed to examine the mRNA and protein levels SIRT6 in human ovarian cancer tissues and normal tissues. The proliferation of ovarian cancer cells was determined using MTT methods. Small interfering RNA (siRNA) technology was used to down-regulate the expression of SIRT6 and Notch 3.

Results: We found that the SIRT6 expression was significantly reduced in human ovarian cancer tissues compared to the normal tissues. Furthermore, our data showed that overexpression of SIRT6 inhibited the proliferation of ovarian cancer cells SKOV3 and OVCAR3. By contrast, down-regulation of SIRT6 enhanced ovarian cancer cells growth. In addition, our study showed that SIRT6 suppressed the expression of Notch 3 both at the mRNA and protein levels in ovarian cancer cells.

Conclusions: Our findings indicated that SIRT6 inhibited the proliferation of ovarian cancer cells through down-regulation of Notch 3 expression, and might provide novel therapeutic targets for ovarian cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Down-Regulation
  • Female
  • Humans
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Notch3
  • Receptors, Notch / biosynthesis*
  • Receptors, Notch / genetics
  • Sirtuins / biosynthesis*
  • Sirtuins / genetics

Substances

  • NOTCH3 protein, human
  • RNA, Messenger
  • Receptor, Notch3
  • Receptors, Notch
  • SIRT6 protein, human
  • Sirtuins