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

• 5-FU–resistant colon cancer cell expressed higher level of ER stress–related proteins.
• It exhibited intense ER staining and mitochondrial Ca2+ overload.
• 5-FU resistance is associated with ER stress in colon cancer.

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.