Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran.
Mol Biol Rep. 2014 Jan;41(1):459-66. doi: 10.1007/s11033-013-2880-0. Epub 2013 Nov 29.
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.
癌胚抗原（CEA）的表达已被证明可以保护癌细胞免受细胞凋亡和失巢凋亡的影响。本研究旨在进一步阐明 CEA 表达在人结直肠癌（CRC）中对抗癌药物耐药性的作用。我们转染了 CEA 阴性的 CRC 细胞系 SW742 以及 CHO 细胞以过表达 CEA，并通过 MTT 法评估它们的化疗耐药性。与亲本细胞系相比，转染细胞对 5-氟尿嘧啶（5-FU）的耐药性显著增加。结果还表明，CEA 表达细胞中细胞 CEA 蛋白的量与 5-FU 耐药性之间存在直接相关性。我们发现 CEA 转染细胞与对照亲本细胞对顺铂和甲氨蝶呤的敏感性无显著差异。我们还比较了 4 种 CRC 细胞系中 CEA 表达与化疗耐药性的关系，这些细胞系在 CEA 产生水平上存在差异。这些细胞系的单层培养物中 CEA 表达水平与 5-FU 耐药性无关。然而，随着药物浓度的增加，5-FU 处理导致耐药亚群细胞的选择，这些细胞显示出 CEA 表达水平的增加。我们分析了 5-FU 在来自两个 CRC 细胞系 LS180 和 HT29/219 的 3D 多细胞培养物中的作用。与单层培养相比，两种细胞系的 CEA 产生和 5-FU 耐药性均受到 3D 生长的刺激。与亲本 CHO 的 3D 球体相比，我们观察到 CEA 表达 CHO 转染子的 3D 培养物中 5-FU 耐药性显著升高。我们的研究结果表明，CEA 水平可能是预测 CRC 患者对基于 5-FU 的化疗反应的合适生物标志物。
