Restoring apoptosis dysregulation using survivin inhibitor in nasopharyngeal cancer.

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.