Interferon β improves the efficacy of low dose cisplatin by inhibiting NF-κB/p-Akt signaling on HeLa cells

Biomed Pharmacother. 2016 Aug:82:124-32. doi: 10.1016/j.biopha.2016.04.058. Epub 2016 May 8.

Abstract

The purpose of this study was to evaluate the anticancer efficacy of interferon β in combination with low dose of cisplatin on human cervical cancer progression, as well as its principal action mechanism. The combination treatment synergistically potentiated the effect of interferon β on cell growth inhibition and DNA damage on HeLa cells by repressing NF-κB/p-Akt signaling. Synergistic targeting of these pathways has a therapeutic potential. Further, the combination treatment ameliorated the expression of pro-apoptotic Bax, and decreased the expression of anti-apoptotic protein Bcl-2. Additionally, the expression of active PARP was significantly increased and MMP-9 level was decreased in combination group as compared to the expression seen for the treatment with interferon β or cisplatin alone. Results demonstrate that the synergistic inhibitory effects of interferon β and low dose of cisplatin on human cervical cancer cells and also suggest that the inhibition of NF-κB/p-Akt signaling pathway plays a critical role in the anticancer effects of combination treatment along with the induction of PARP. Therefore, the combination of interferon β and cisplatin may be a useful treatment for human cervical cancer, with a greater effectiveness than other treatments.

Keywords: Akt; Chemosensitivity; Cisplatin; Interferon β; NF-κB; PARP.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • HeLa Cells
  • Humans
  • I-kappa B Proteins / metabolism
  • Interferon-beta / pharmacology*
  • Matrix Metalloproteinase 9 / metabolism
  • Micronucleus, Germline / drug effects
  • Micronucleus, Germline / metabolism
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • STAT2 Transcription Factor / metabolism
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • I-kappa B Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • STAT2 Transcription Factor
  • Interferon-beta
  • Poly(ADP-ribose) Polymerases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9
  • Cisplatin