Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer
Junli Shi1, Soo Yee Tan2, Andrea Zhe Ern Lee3
1Institute of Bioengineering and Nanotechnology, Singapore.
Background:
Restoring apoptosis dysregulation via survivin inhibition has been investigated in several cancers. In Epstein-Barr Virus (EBV)-driven nasopharyngeal cancer (NPC), virally induced oncogenes can upregulate survivin. Therefore, we seek to investigate the therapeutic efficacy of YM-155 (a survivin inhibitor) in NPC, both in vitro and in vivo models.
Methods:
Cytotoxicity, apoptosis, and active-caspase 3 expression assays were performed.
Results:
Both NPC tissue and cells expressed high levels of survivin which were inhibited by YM-155 in a dose-dependent manner. In addition, YM-155 induced apoptosis of NPC cells with an IC50 of 100 nM and inhibited tumor growth in vivo (P < 0.05). YM-155 in combination with cisplatin or radiation significantly increased overall cytotoxicity as compared to YM-155 monotherapy. In the xenograft model, YM-155 plus radiation additively achieved significantly higher percentage of active-caspase 3-positive tumor cells than radiation alone (P < 0.05).
Conclusions:
YM-155 is a potential therapeutic agent for NPC through inhibiting survivin and restoring apoptosis dysregulation.
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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