carcinoembryonic antigen expression and resistance to radiation-and 5-fluorouracil-induced apoptosis and autophagy
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abstract
understanding the mechanism of tumor resistance is critical for cancer therapy. in this study, we investigated the effect of carcinoembryonic antigen (cea) overexpression on uv-and 5-fluorouracil (5-fu)-induced apoptosis and autophagy in colorectal cancer cells. we used histone deacetylase (hdac) inhibitor, nab and dna demethylating agent, 5- azacytidine (5-aza) to induce cea expression in ht29/219 and sw742 colorectal cancer cell lines. mtt assay was used to measure ic50 value of the cells exposed to graded concentrations of 5- fu with either 0.1 mm nab or 1 μm 5-aza for 72 h . using cho- and sw742-cea transfectants, we also investigated the effect of cea expression on uv- and 5-fu-induced apoptosis and autophagy. treatment of ht29/219 cell line with nab and 5-aza increased cea expression by 29% and 31%, respectively. compared with control cells, the ic50 value for 5-fu of nab and 5-aza-treated cells increased by 40% and 57%, respectively. treatment of sw742 cells with nab or 5-aza increased neither cea expression nor the ic50 value for 5-fu. in comparison to parental cells, cea expression also significantly protected transfected cells against uv-induced apoptosis. decreased proportions of autophagy and apoptosis were also observed in 5-fu treated sw742- and cho-cea transfectants. we conclude that cea expression can effectively protect colorectal cancer cells against radiation and drug-induced apoptosis and autophagy.
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Journal title:
international journal of molecular and cellular medicineجلد ۵، شماره ۲، صفحات ۸۰-۸۹
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