Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer

Br J Cancer. 2011 Oct 11;105(8):1210-7. doi: 10.1038/bjc.2011.348. Epub 2011 Sep 6.


Background: Activin A is a multi-functional cytokine belonging to the transforming growth factor-β (TGF-β) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that inhibin β A subunit (INHBA) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.

Methods: Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs) in vitro and a stable INHBA-introduced GC cell line in vivo.

Results: Compared with TGF-β, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable INHBA-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis in vivo.

Conclusion: Our findings highlight the suppressive role of activin A, unlike TGF-β, on tumour growth and angiogenesis in GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / physiology*
  • Animals
  • Base Sequence
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / prevention & control*
  • Phosphorylation
  • Smad2 Protein / metabolism
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA Primers
  • Smad2 Protein
  • Vascular Endothelial Growth Factor A
  • activin A
  • Activins