Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism

Int J Mol Sci. 2016 Dec 19;17(12):2139. doi: 10.3390/ijms17122139.

Abstract

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC.

Keywords: NF-κB; ionizing radiation; nasopharyngeal carcinoma; phosphorylation; triptolide.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Diterpenes / therapeutic use*
  • Epoxy Compounds / therapeutic use
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Phenanthrenes / therapeutic use*
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Transcription Factor RelA / antagonists & inhibitors*
  • Transcription Factor RelA / biosynthesis*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Xenograft Model Antitumor Assays / methods
  • bcl-2-Associated X Protein / biosynthesis

Substances

  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • Proto-Oncogene Proteins c-bcl-2
  • RELA protein, human
  • Transcription Factor RelA
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • triptolide