TY - JOUR T1 - GRP78 Regulates Apoptosis, Cell Survival and Proliferation in 5-Fluorouracil-resistant SNUC5 Colon Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 4943 LP - 4951 VL - 37 IS - 9 AU - JUN HEE LEE AU - YEO MIN YOON AU - SANG HUN LEE Y1 - 2017/09/01 UR - http://ar.iiarjournals.org/content/37/9/4943.abstract N2 - 5-Fluorouracil (5-FU) is an effective anticancer drug. However, the development of drug resistance has limited its chemotherapeutic efficacy. To address this problem, we investigated the expression of glucose-regulated protein (GRP78, 78 kDa) in 5-FU-resistant colorectal cancer (CRC) cells (SNUC5/5FUR). GRP78 was highly expressed in the SNUC5/5FUR cells compared to wild-type SNUC5 cells. In the presence of 5-FU, GRP78 knockdown induced apoptosis via activation of caspase-3 and poly(ADP-ribose)-polymerase 1. GRP78 also inhibited the production of intracellular reactive oxygen species by regulating stress-associated signaling pathways. Furthermore, GRP78 enhanced cell survival and proliferation via activation of the phosphatidylinosito-3-kinase–AKT–mammalian target of rapamycin axis and cell cycle-associated proteins. These effects were blocked upon GRP78 knockdown, which indicates that GRP78 is involved in the development of 5-FU resistance in these CRC cells. Therefore, a combination of chemotherapy and GRP78-specific targeting may counteract 5-FU resistance in CRC cells. ER -