Inhibitory effects of extracellular adenosine triphosphate on growth of esophageal carcinoma cells

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 intemudeosomal 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.

Earlier onset and multiple primaries in familial as opposed to sporadic esophageal cancer

AIM: To study the differences in onset age and multiple primary cancers between familial and sporadic esophageal squamous cell carcinoma(ESCC).METHODS: The differences in onset age and multiple primary cancers were analyzed between ESCC patients with(n = 766) and without(n = 1776) a family history of the cancer. The cases analyzed constituted all consecutive patients who had undergone cure-intent surgery at the Department of Thoracic Surgery of the 4th Hospital of Hebei Medical University from January 1 1975 to December 31 1989. Because we also originally aimed to examine the difference in survival time, only older subjects with a long follow-up period were selected.RESULTS: Overall, patients with ESCC and a positive family history of the cancer had a significantly younger age at onset and more multiple primary cancers than those without a positive family history(51.83 ± 8.39 vs 53.49 ± 8.23 years old, P = 0.000; 5.50% vs 1.70%, P = 0.000). Both of these differences were evident in subgroup analyses, however, no correlations were observed. While age at onset differed significantly by family history in males, smokers, and drinkers, the difference in multiple primary cancers by family history was significant in nonsmoking, nondrinking, and younger onset patients. In multivariate analysis, age over 50 years, tobacco smoking, and multiple primary cancers were found to be significant predictors of familial cancer: the corresponding OR(95%CI) and P-value were 0.974(0.963-0.985) and 0.000; 1.271(1.053-1.535) and 0.012; and 4.265(2.535-7.176) and 0.000, respectively.CONCLUSION: Patients with ESCC and a positive family history of the cancer had a significantly younger onset age and more multiple primary cancers than those without a positive family history. Sub-group analyses indicated that younger onset age may be due to the interaction of genetic predisposition and environmental hazards, and multiple primary cancers may only be due to genetic predisposition.