Effect of annexin A7 suppression on the apoptosis of gastric cancer cells

Mol Cell Biochem. 2017 May;429(1-2):33-43. doi: 10.1007/s11010-016-2934-4. Epub 2017 Feb 7.

Abstract

Understanding the molecular mechanism of gastric cancer cell apoptosis is pivotal for the development of precise therapies targeting this disease. In the present study, we examined the effects of annexin A7 inhibition on the apoptosis of gastric cancer cells and the growth of tumour xenografts in vivo. Expression of annexin A7 in BGC823 cells was suppressed by small interference RNA, and cells apoptosis was assessed by flow cytometry. The mechanism by which annexin A7 mediates apoptosis in BGC823 cells was explored by determining the expression of key apoptosis regulators. In addition, by suppressing annexin A7 in BGC823 cells with small hairpin RNA, we studied the effects of annexin A7 inhibition on in vivo tumour growth. Our results showed that inhibiting annexin A7 expression induced more than fivefold increase in BGC823 cell apoptosis in vitro. This was in concord with a significant decrease of Bcl-2 expression and increases of Bax, Caspase-3, and Caspase-9. The activities of caspase-3 and caspase-9 were increased by 2.95 ± 0.18 and 3.70 ± 0.33 times, respectively, upon the annexin A7 downregulation in BGC823 cells. Importantly, suppressing annexin A7 showed the same apoptotic mechanism in vivo and significantly inhibited the growth of BGC823 xenografts in mice. These data suggest that annexin A7 likely protects gastric cells from apoptosis and targeting it may represent a valuable strategy in future therapeutic development.

Keywords: Annexin A7; Apoptosis; Gastric cancer; RNA interference.

MeSH terms

  • Animals
  • Annexin A7 / drug effects
  • Annexin A7 / genetics*
  • Apoptosis
  • Apoptosis Regulatory Proteins / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Neoplasm Transplantation
  • RNA, Small Interfering / pharmacology*
  • Stomach Neoplasms / genetics*

Substances

  • Annexin A7
  • Anxa7 protein, mouse
  • Apoptosis Regulatory Proteins
  • RNA, Small Interfering