Esophageal Cancer
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2005; 11(38): 5915-5919
Published online Oct 14, 2005. doi: 10.3748/wjg.v11.i38.5915
Inhibitory effects of extracellular adenosine triphosphate on growth of esophageal carcinoma cells
Ming-Xia Wang, Lei-Ming Ren, Bao-En Shan
Ming-Xia Wang, Bao-En Shan, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Lei-Ming Ren, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Science and Technology Development Project of Hebei Province, No. 032761192
Correspondence to: Lei-Ming Ren, MD, PhD, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China. ren-leiming@263.net
Telephone: +86-311-6034579 Fax: +86-311-6077634
Received: December 28, 2004
Revised: March 23, 2005
Accepted: March 24, 2005
Published online: October 14, 2005
Abstract

AIM: To study the growth inhibitory effects of ATP on TE-13 human squamous esophageal carcinoma cells in vitro.

METHODS: MTT assay was used to determine the inhibition of proliferation of ATP or adenosine (ADO) on TE-13 cell line. The morphological changes of TE-13 cells induced by ATP or ADO were observed under fluorescence light microscope by acridine orange (AO)/ethidium bromide (EB) double stained cells. The internucleosomal fragmentation of genomic DNA was detected by agarose gel electrophoresis. The apoptotic rate and cell cycle after treatment with ATP or ADO were determined by flow cytometry.

RESULTS: ATP and ADO produced inhibitory effects on TE-13 cells at the concentration between 0.01 and 1.0 mmol/L. The IC50 of TE-13 cells exposed to ATP or ADO for 48 and 72 h was 0.71 or 1.05, and 0.21 or 0.19 mmol/L, respectively. The distribution of cell cycle phase and proliferation index (PI) value of TE-13 cells changed, when being exposed to ATP or ADO at the concentrations of 0.01, 0.1, and 1 mmol/L for 48 h. ATP and ADO inhibited the cell proliferation by changing the distribution of cell cycle phase via either G0/G1 phase (ATP or ADO, 1 mmol/L) or S phase (ATP, 0.1 mmol/L) arrest. Under light microscope, the tumor cells exposed to 0.3 mmol/L ATP or ADO displayed morphological changes of apoptosis. A ladder-like pattern of DNA fragmentation was obtained from TE-13 cells treated with 0.1-1 mmol/L ATP or ADO in agarose gel electrophoresis. ATP and ADO induced apoptosis of TE-13 cells in a dose-dependent manner at the concentration between 0.03 and 1 mmol/L. The maximum apoptotic rate of TE-13 cells exposed to ATP or ADO for 48 h was 16.63% or 16.9%, respectively.

CONCLUSION: ATP and ADO inhibit cell proliferation, arrest cell cycle, and induce apoptosis of TE-13 cell line.

Keywords: Extracellular adenosine triphosphate; Esophageal carcinoma cells; Apoptosis; Growth inhibition