title: Carcinoembryonic Antigen Expression and Resistance to Radiation and 5-Fluorouracil-Induced Apoptosis and Autophagy.
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.
authors.affiliation: Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.; Autoimmune Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.; Current address: Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eftekhar
authors.affiliation: Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.
authors.forename: Hajar
authors.initials: H
authors.lastname: Jaberie
authors.affiliation: Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.; Autoimmune Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.
authors.forename: Fakhraddin
authors.initials: F
authors.lastname: Naghibalhossaini
keywords: 5-fluorouracil; Carcinoembryonic antigen (CEA); apoptosis; autophagy; colorectal cancer