Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

Zafar Gholinejad, Nejat kheiripour, Mitra Nourbakhsh, Davod Ilbeigi, Kiarash Behroozfar, Zahra Hesari, Abolfazl Golestani, Mohammad Shabani, Nahid Einollahi

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62 Citations (Scopus)

Abstract

Background Visfatin is a novel adipokine and proinflammatory cytokine which is implicated in breast cancer progression. The exact proliferative and anti-apoptotic mechanisms of visfatin are still under debate. In this study, the effect of extracellular visfatin on proliferation and apoptosis of breast cancer cells were investigated considering key regulatory molecules in these procedures. Methods BrdU (Bromodeoxyuridine) experiment was used to assess cell proliferation in response to visfatin treatment. Cell viability and apoptosis were assessed using MTT assay and flowcytometry, respectively. Phosphorylation levels of AKT and ERK1/2 as well as survivin levels and Poly ADP ribose polymerase (PARP) cleavage were investigated by western blot analysis. Results Visfatin induced proliferation of MCF-7 and MDA-MB-231 cells, an effect that was repressed by using AKT and ERK1/2 inhibitors, indicating involvement of these two signaling pathways in the proliferative effect of visfatin. Similarly, phosphorylation of AKT and ERK1/2 were elevated by visfatin treatment. On the other hand, visfatin improved cell viability and prevented TNF-α-induced apoptosis as well as PARP cleavage. Visfatin also exerted a protective effect on survivin. Conclusion The results of this study suggest that visfatin induces breast cancer cell proliferation through AKT/PI3K and ERK/MAPK activation and protects against apoptosis in these cells. Thus increased visfatin levels may augment breast cancer development and attenuate treatment efficiency in breast cancer patients.

Original languageEnglish
Pages (from-to)9-15
Number of pages7
JournalPeptides
Volume92
DOIs
Publication statusPublished - 1 Jun 2017
Externally publishedYes

Keywords

  • AKT
  • Apoptosis
  • Breast cancer
  • ERK1/2
  • Survivin
  • Visfatin

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