Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer

Junli Shi1, Soo Yee Tan2, Andrea Zhe Ern Lee3

  • 1Institute of Bioengineering and Nanotechnology, Singapore.

Head & Neck
|January 12, 2020
PubMed
Abstract

Insights

Survivin inhibition with YM-155 shows promise for nasopharyngeal cancer (NPC) treatment. This survivin inhibitor effectively induced apoptosis and reduced tumor growth, offering a new therapeutic avenue for NPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Survivin is frequently upregulated in Epstein-Barr Virus (EBV)-driven nasopharyngeal cancer (NPC) due to oncogenic factors.
  • Restoring apoptosis via survivin inhibition is a therapeutic strategy explored in various cancers.

Purpose of the Study:

  • To investigate the therapeutic potential of YM-155, a survivin inhibitor, in both in vitro and in vivo models of nasopharyngeal cancer.
  • To evaluate the efficacy of YM-155 as a monotherapy and in combination with standard treatments like cisplatin and radiation.

Main Methods:

  • Assays for cytotoxicity and apoptosis were conducted.
  • Active-caspase 3 expression was measured to assess apoptosis.
  • In vivo efficacy was evaluated in a xenograft model.

Main Results:

  • YM-155 demonstrated dose-dependent inhibition of survivin in NPC tissues and cells.
  • YM-155 induced NPC cell apoptosis with an IC50 of 100 nM and inhibited tumor growth in vivo.
  • Combination therapy (YM-155 with cisplatin or radiation) significantly enhanced cytotoxicity compared to YM-155 alone. YM-155 plus radiation additively increased active-caspase 3 expression in xenografts.

Conclusions:

  • YM-155 shows potential as a therapeutic agent for nasopharyngeal cancer by inhibiting survivin.
  • YM-155 effectively restores apoptosis dysregulation in NPC models.
  • Combination strategies involving YM-155 may offer improved therapeutic outcomes for NPC patients.

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