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Environ Toxicol Pharmacol. 2016 Jun;44:128-33. doi: 10.1016/j.etap.2016.05.005. Epub 2016 May 4.

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

Author information

1
Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea.
2
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
3
School of Medicine, Jeju National University, Jeju 63241, Republic of Korea.
4
School of Medicine, Jeju National University, Jeju 63241, Republic of Korea. Electronic address: suhmok@jejunu.ac.kr.
5
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: jinwonh@jejunu.ac.kr.

Abstract

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 Ca(2+) 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.

KEYWORDS:

5-FU resistance; ER stress; ER stress-related proteins; Extracellular signal-regulated kinases; Human colon cancer cells

PMID:
27163731
DOI:
10.1016/j.etap.2016.05.005
[Indexed for MEDLINE]

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