NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression
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 i...
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/13/4646 |
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| author | Eui Joo Kim Yoon Jae Kim Hye In Lee Seok-Hoo Jeong Hyo Jung Nam Jae Hee Cho |
| author_facet | Eui Joo Kim Yoon Jae Kim Hye In Lee Seok-Hoo Jeong Hyo Jung Nam Jae Hee Cho |
| author_sort | Eui Joo Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:47:59Z |
| format | Article |
| id | doaj.art-fa72b54e77494c9da9a5287e8b8272c4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:47:59Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fa72b54e77494c9da9a5287e8b8272c42023-11-20T05:24:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012113464610.3390/ijms21134646NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 ExpressionEui Joo Kim0Yoon Jae Kim1Hye In Lee2Seok-Hoo Jeong3Hyo Jung Nam4Jae Hee Cho5Division of Gastroenterology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Catholic Kwandong University International St. Mary’s Hospital, Incheon 22711, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, KoreaDivision of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaChemoresistance 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.https://www.mdpi.com/1422-0067/21/13/4646pancreatic cancer5-FluorouracilchemoresistanceNF-E2-related factor 2 |
| spellingShingle | Eui Joo Kim Yoon Jae Kim Hye In Lee Seok-Hoo Jeong Hyo Jung Nam Jae Hee Cho NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression International Journal of Molecular Sciences pancreatic cancer 5-Fluorouracil chemoresistance NF-E2-related factor 2 |
| title | NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression |
| title_full | NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression |
| title_fullStr | NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression |
| title_full_unstemmed | NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression |
| title_short | NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression |
| title_sort | nrf2 knockdown resensitizes 5 fluorouracil resistant pancreatic cancer cells by suppressing ho 1 and abcg2 expression |
| topic | pancreatic cancer 5-Fluorouracil chemoresistance NF-E2-related factor 2 |
| url | https://www.mdpi.com/1422-0067/21/13/4646 |
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