Arsenic trioxide induced the apoptosis of laryngeal cancer via down-regulation of survivin mRNA

Auris Nasus Larynx. 2008 Mar;35(1):95-101. doi: 10.1016/j.anl.2007.07.009. Epub 2007 Sep 14.

Abstract

Objective: Arsenic trioxide (As(2)O(3)) is used clinically to treat acute promyelocytic leukemia and has activity in vitro against several solid tumor cell lines, where induction of differentiation and apoptosis are the prime effects. As a novel anticancer agent for treatment of solid cancers, As(2)O(3) is promising and the mechanism has been not still fully understood. Laryngeal squamous cell carcinoma (LSCC) is one common tumor in head and neck cancers. The objective of this study was to investigate the effects of As(2)O(3) on LSCC cell line HEP-2, and their possible involvement in As(2)O(3)-induced apoptosis.

Methods: The cell viability was analyzed by MTT assay method and the morphological changes were observed by an inverted microscope and acridine orange (AO) staining. The caspase-3 activity was measured by a fluorophotometer. The expression of survivin mRNA was evaluated by RT-PCR.

Results: In this study, we demonstrated an apoptotic effect of As(2)O(3) in LSCC cell line Hep-2. In Hep-2 cells, As(2)O(3) decreased the cell viability, inhibited the growth and proliferation, induced apoptosis and increased the activity of caspase-3 in a dose-dependent manner. And the expression of survivin mRNA was also decreased in a dose-dependent manner.

Conclusion: We concluded that As(2)O(3) induced the apoptosis of Hep-2 cells via down-regulating the expression of survivin mRNA.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / analysis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects*
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Laryngeal Neoplasms / pathology
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Oxides / pharmacology*
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Tumor Cells, Cultured / drug effects*
  • Tumor Cells, Cultured / pathology

Substances

  • Antineoplastic Agents
  • Arsenicals
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Oxides
  • RNA, Messenger
  • Survivin
  • Caspase 3
  • Arsenic Trioxide