Brief Article
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World J Gastroenterol. May 14, 2014; 20(18): 5505-5510
Published online May 14, 2014. doi: 10.3748/wjg.v20.i18.5505
Arsenic trioxide induces apoptosis of human gastrointestinal cancer cells
Zhi-Bin Ma, Hong-Yu Xu, Miao Jiang, You-Lin Yang, Lian-Xin Liu, Ying-Hua Li
Zhi-Bin Ma, Hong-Yu Xu, Miao Jiang, You-Lin Yang, Lian-Xin Liu, Department of Gastroenterology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Ying-Hua Li, Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Author contributions: Ma ZB and Xu HY contributed equally to this study, and are co-first authors; Ma ZB and Xu HY were responsible for statistical analysis of the data; Jiang M was responsible for the immunohistochemistry analysis; Yang YL was responsible for pre-treatment sample collection and specimen collection; Liu LX was responsible for clinical use; Li YH was the main designer of this study.
Supported by The Heilongjiang Provincial Natural Science Foundation of China, No. D2006-51
Correspondence to: Ying-Hua Li, MD, PhD, Department of Hematology, First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, China. mazhibin1973117@126.com
Telephone: +86-451-85555119 Fax: +86-451-85555119
Received: October 13, 2013
Revised: February 2, 2014
Accepted: March 6, 2014
Published online: May 14, 2014
Processing time: 212 Days and 14.3 Hours
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: Gastrointestinal cancer; Arsenic trioxide; Apoptosis; p53; Bcl-2

Core tip: In this study, patients with gastrointestinal cancer were treated with arsenic trioxide for the first time. The use of arsenic trioxide in neoadjuvant chemotherapy prior to surgery improved surgical results.