Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells

Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells
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DOI:
10.1016/j.etap.2016.05.005
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发表时间:
2016-06-01
影响因子:
4.3
通讯作者:
Hyun, Jin Won
Hyun, Jin Won
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Kim, Joon Ki;Kang, Kyoung Ah;Hyun, Jin Won

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结肠癌可以用5-氟尿嘧啶(5-FU)治疗,但经常发生5-FU耐药性。我们确定5-FU耐药性是否由内质网(ER)应激引起。5- fu耐药SNUC5结肠癌细胞(SNUC5/FUR细胞)比药物敏感的SNUC5细胞表达更高水平的内质网应激相关蛋白。SNUC5/FUR细胞也表现出更强烈的ER染色和更高水平的线粒体Ca2+超载。用siRNA转染GRP78、ATF6、ERK或AKT的SNUC5/FUR细胞比对照rna转染的细胞对5-FU更敏感。这些结果表明5-FU耐药性与结肠癌内质网应激有关。(C) 2016 Elsevier B.V.版权所有
Colon cancer can be treated with 5-fluorouracil (5-FU), but 5-FU resistance frequently occurs. We determined whether 5-FU resistance arises as a result of endoplasmic reticulum (ER) stress. 5-FU-resistant SNUC5 colon cancer cells (SNUC5/FUR cells) expressed higher levels of ER stress-related proteins than drug-sensitive SNUC5 cells. SNUC5/FUR cells also exhibited more intense ER staining and higher level of mitochondrial Ca2+ overload. SNUC5/FUR cells transfected with siRNA against GRP78, ATF6, ERK, or AKT were more sensitive to 5-FU than siControl RNA-transfected cells. These results suggested that 5-FU resistance was associated with ER stress in colon cancer. (C) 2016 Elsevier B.V. All rights reserved.