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

Publication date: Available online 4 May 2016 Source:Environmental Toxicology and Pharmacology Author(s): Joon Ki Kim, Kyoung Ah Kang, Mei Jing Piao, Yea Seong Ryu, Xia Han, Pattage Madushan Dilhara Jayatissa Fernando, Min Chang Oh, Jeong Eon Park, Kristina Shilnikova, Sun Jin Boo, Soo-Young Na, Yong Joo Jeong, Seung Uk Jeong, Jin Won Hyun 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.
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research