Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

  • Authors:
    • Shu Yang
    • Shi‑Sheng Li
    • Xin‑Ming Yang
    • Dan‑Hui Yin
    • Lin Wang
  • View Affiliations

  • Published online on: May 5, 2016     https://doi.org/10.3892/ol.2016.4522
  • Pages: 4167-4176
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Abstract

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in the majority of tumor cells, whilst sparing normal cells. However, the potential use of TRAIL in the treatment of cancer is limited by the inevitable emergence of drug resistance. The present study reports the upregulation of latent membrane protein 1 (LMP1)-induced TRAIL resistance via the enhanced expression of X‑linked inhibitor of apoptosis protein (XIAP) in nasopharyngeal carcinoma (NPC) cells. LMP1‑positive NPC cells were indicated to be more sensitive to TRAIL compared with LMP1-negative NPC cells in three NPC cell lines. CNE‑1 is a LMP1‑negative NPC cell line that was transfected with pGL6-LMP1; following which, sensitivity to TRAIL decreased. LMP1‑induced TRAIL resistance was associated with the decreased cleavage of caspase‑8,‑3 and ‑9, BH3 interacting domain death agonist (Bid) and mitochondrial depolarization, without any effects on the expression of the death receptors, B‑cell lymphoma (Bcl)‑2 and Bcl-extra long. Knockdown of XIAP with small interfering RNA increased caspase‑3 and ‑9 and Bid cleavage, and prevented LMP1‑induced TRAIL resistance. Furthermore, embelin, the inhibitor of XIAP, prevented LMP1‑induced TRAIL resistance in the Epstein‑Barr virus (EBV)‑positive CNE‑1‑LMP1 and C666‑1 NPC cell lines. However, embelin did not enhance TRAIL‑induced apoptosis in NP‑69, which was used as a benign nasopharyngeal epithelial cell line. These data show that LMP1 inhibits TRAIL‑mediated apoptosis by upregulation of XIAP. Embelin may be used in an efficacious and safe manner to prevent LMP1‑induced TRAIL resistance. The present study may have implications for the development and validation of novel strategies to prevent TRAIL resistance in EBV-positive NPC.
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June-2016
Volume 11 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Yang S, Li SS, Yang XM, Yin DH and Wang L: Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells. Oncol Lett 11: 4167-4176, 2016
APA
Yang, S., Li, S., Yang, X., Yin, D., & Wang, L. (2016). Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells. Oncology Letters, 11, 4167-4176. https://doi.org/10.3892/ol.2016.4522
MLA
Yang, S., Li, S., Yang, X., Yin, D., Wang, L."Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells". Oncology Letters 11.6 (2016): 4167-4176.
Chicago
Yang, S., Li, S., Yang, X., Yin, D., Wang, L."Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells". Oncology Letters 11, no. 6 (2016): 4167-4176. https://doi.org/10.3892/ol.2016.4522