NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression

Autor: Eui Joo Kim, Yoon Jae Kim, Seok Hoo Jeong, Hyo Jung Nam, Hye In Lee, Jae Hee Cho
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Abcg2
endocrine system diseases
pancreatic cancer
Antioxidants
lcsh:Chemistry
0302 clinical medicine
Cell Movement
ATP Binding Cassette Transporter
Subfamily G
Member 2
lcsh:QH301-705.5
Spectroscopy
Gene knockdown
biology
Chemistry
chemoresistance
General Medicine
Neoplasm Proteins
Computer Science Applications
Gene Expression Regulation
Neoplastic
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Fluorouracil
Carcinoma
Pancreatic Ductal
Homeobox protein NANOG
Epithelial-Mesenchymal Transition
Cell Survival
5-Fluorouracil
SOD2
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Cell Line
Tumor
Pancreatic cancer
medicine
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Physical and Theoretical Chemistry
Pancreas
Molecular Biology
NF-E2-related factor 2
Organic Chemistry
medicine.disease
Pancreatic Neoplasms
Heme oxygenase
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Drug Resistance
Neoplasm
Cell culture
Cancer research
biology.protein
ATP-Binding Cassette Transporters
Heme Oxygenase-1
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 13
International Journal of Molecular Sciences, Vol 21, Iss 4646, p 4646 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21134646
Popis: Chemoresistance is a leading cause of morbidity and mortality in patients with pancreatic cancer and remains an obstacle to successful treatment. The antioxidant transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (NRF2), which plays important roles in tumor angiogenesis and invasiveness, is upregulated in pancreatic ductal adenocarcinoma (PDAC), where it correlates with poor survival. Here, we investigated the role of NRF2 in two 5-Fluourouracil-resistant (5-FUR) PDAC cell lines: BxPC-3 and CFPAC-1. Levels of NRF2 and antioxidants, such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase 2 (SOD2), were higher in the chemoresistant cells than in their chemosensitive counterparts. Expression of epithelial mesenchymal transition (EMT) markers, stemness markers, including Nanog, Oct4, and CD133, and that of the drug transporter ATP binding cassette, subfamily G, member A2 (ABCG2) was also upregulated in 5-FUR PDAC cells. NRF2 knockdown reversed 5-FU resistance of PDAC cells via suppression of ABCG2 and HO-1. In summary, these data indicate that NRF2 is a potential target for resensitizing 5-FUR PDAC cells to 5-FU to improve treatment outcomes in patients with pancreatic cancer.
Databáze: OpenAIRE
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