Arsenic trioxide induces apoptosis of human gastrointestinal cancer cells

World J Gastroenterol. 2014 May 14;20(18):5505-10. doi: 10.3748/wjg.v20.i18.5505.

Abstract

Aim: To investigate the changes in apoptosis in gastrointestinal cancer cells from patients with gastrointestinal cancers treated with arsenic trioxide (As₂O₃); and to study the possible molecular mechanisms of such changes by detecting the expression levels of p53 and Bcl-2.

Methods: Twenty patients with gastrointestinal adenocarcinoma based on endoscopic and biopsy findings (ten patients with gastric cancer and ten patients with colorectal cancer) who received treatment in our hospital between August 2007 and December 2008 were included in this study. None of the patients had received anti-tumour agents prior to As₂O₃ treatment. As₂O₃ was administered intravenously at a dose of 0.01 g/d diluted with 5% glucose in normal saline for 2-3 h for 3 consecutive days before surgery. Morphological changes associated with apoptosis of gastrointestinal cancer cells were observed by light microscopy. Changes in the apoptotic index induced by As₂O₃ were investigated using the terminal deoxynucleotidyl transferase dUTP nick end labelling method. Expression levels of p53 and Bcl-2 proteins in gastrointestinal cancer tissues were determined by immunohistochemistry.

Results: The apoptotic index of human gastrointestinal cancer cells was higher in cells from patients treated with As₂O₃ than in those not treated (P < 0.05). p53 protein expression in gastrointestinal tissues was unchanged by As₂O₃ (P > 0.05). However, Bcl-2 protein expression in gastrointestinal tissues was down-regulated by As₂O₃ (P < 0.01).

Conclusion: These results demonstrate that As₂O₃ treatment in patients with gastrointestinal cancers can induce apoptosis in gastrointestinal cancer cells and down-regulate Bcl-2 protein expression.

Keywords: Apoptosis; Arsenic trioxide; Bcl-2; Gastrointestinal cancer; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / administration & dosage*
  • Arsenicals / adverse effects
  • Biomarkers, Tumor / metabolism
  • Drug Administration Schedule
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / pathology
  • Humans
  • Infusions, Intravenous
  • Oxides / administration & dosage*
  • Oxides / adverse effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Biomarkers, Tumor
  • Oxides
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Arsenic Trioxide