title: Carcinoembryonic antigen expression level as a predictive factor for response to 5-fluorouracil in colorectal cancer.
abstract: Carcinoembryonic antigen (CEA) expression has been shown to protect cancer cell lines from apoptosis and anoikis. The aim of this study was to further elucidate the role of CEA expression on resistance to anticancer drugs in human colorectal cancer (CRC). We transfected CEA negative CRC cell line SW742 as well as CHO cells to overexpress CEA and their chemoresistance were assessed by MTT assay. In comparison to the parental cell lines, transfected cells had significantly increased resistance to 5-fluorouracil (5-FU). The results also showed a direct correlation between the amount of cellular CEA protein and 5-FU resistance in CEA expressing cells. We found no significant difference in sensitivity to cisplatin and methotrexate between CEA-transfected cells and their counter parental cells. We also compared the association between CEA expression and chemoresistance of 4 CRC cell lines which differed in the levels of CEA production. The CEA expression levels in monolayer cultures of these cell lines did not correlate with the 5-FU resistance. However, 5-FU treatment resulted in the selection of sub-populations of resistant cells that displayed increased CEA expression levels by increasing drug concentration. We analyzed the effect of 5-FU in a 3D multicellular culture generated from the two CRC cell lines, LS180 and HT29/219. Compared with monolayer culture, CEA production and 5-FU resistance in both cell lines were stimulated by 3D growth. In comparison to the 3D spheroids of parental CHO, we observed a significantly elevated 5-FU resistance in 3D culture of the CEA-expressing CHO transfectants. Our findings suggest that the CEA level may be a suitable biomarker for predicting tumor response to 5-FU-based chemotherapy in CRC.
authors.affiliation: Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Eftekhar
authors.forename: Fakhraddin
authors.initials: F
authors.lastname: Naghibalhossaini
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D016466:CHO Cells; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015179:Colorectal Neoplasms; D006224:Cricetinae; D003412:Cricetulus; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D020128:Inhibitory Concentration 50; D008727:Methotrexate / Q000494:pharmacology; D018874:Spheroids, Cellular / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate