title: Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells.
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.
authors.affiliation: Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea.
authors.forename: Joon Ki
authors.initials: JK
authors.lastname: Kim
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Yea Seong
authors.initials: YS
authors.lastname: Ryu
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Xia
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Pattage Madushan Dilhara Jayatissa
authors.initials: PM
authors.lastname: Fernando
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Min Chang
authors.initials: MC
authors.lastname: Oh
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Park
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Kristina
authors.initials: K
authors.lastname: Shilnikova
authors.affiliation: School of Medicine, Jeju National University, Jeju 63241, Republic of Korea.
authors.forename: Sun Jin
authors.initials: SJ
authors.lastname: Boo
authors.affiliation: School of Medicine, Jeju National University, Jeju 63241, Republic of Korea.
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Na
authors.affiliation: Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea.
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: School of Medicine, Jeju National University, Jeju 63241, Republic of Korea. Electronic address: suhmok@jejunu.ac.kr.
authors.forename: Seung Uk
authors.initials: SU
authors.lastname: Jeong
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: jinwonh@jejunu.ac.kr.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D000964:Antimetabolites, Antineoplastic; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium; D005472:Fluorouracil
keywords: 5-FU resistance; ER stress; ER stress-related proteins; Extracellular signal-regulated kinases; Human colon cancer cells