Abstract |
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.
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Authors | Jun Hee Lee, Yeo Min Yoon, Sang Hun Lee |
Journal | Anticancer research
(Anticancer Res)
Vol. 37
Issue 9
Pg. 4943-4951
(09 2017)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 28870916
(Publication Type: Journal Article)
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Copyright | Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. |
Chemical References |
- Antimetabolites, Antineoplastic
- Endoplasmic Reticulum Chaperone BiP
- HSPA5 protein, human
- Heat-Shock Proteins
- RNA, Small Interfering
- Fluorouracil
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Topics |
- Antimetabolites, Antineoplastic
(pharmacology)
- Apoptosis
(drug effects)
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Colonic Neoplasms
(drug therapy, metabolism, pathology)
- Drug Resistance, Neoplasm
- Endoplasmic Reticulum Chaperone BiP
- Fluorouracil
(pharmacology)
- Heat-Shock Proteins
(antagonists & inhibitors, genetics, metabolism)
- Humans
- RNA, Small Interfering
(genetics)
- Tumor Cells, Cultured
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