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Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells

Department of Cancer Research, Vinmec Research Institute of Stem Cell and Gene Technology, 458 Minh Khai, Hanoi 10000, Vietnam
Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang 59000, Vietnam
Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea
Graduate School of Convergence Medical Science, Dankook University, Cheonan 31116, Korea
Department of Physiology, College of Medicine, Dankook University, Cheonan 31116, Korea
Department of Biochemistry, College of Medicine, Dankook University, Cheonan 31116, Korea
Authors to whom correspondence should be addressed.
Antioxidants 2017, 6(3), 52;
Received: 31 March 2017 / Revised: 15 June 2017 / Accepted: 28 June 2017 / Published: 1 July 2017
(This article belongs to the Special Issue Oxidative Stress and Cancer: The Nrf2 Enigma)
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Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy. We aimed to evaluate the possibility that modulation of NRF2 expression could be effective in the treatment of pancreatic cancer cells. We investigated whether the depletion of NRF2 by using small interfering RNAs (siRNAs) is effective in the expression of biomarkers of pancreatic cancer stemness such as aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1). NRF2 knockdown markedly reduced the expression of NRF2 and glutamate-cysteine ligase catalytic subunit (GCLC) in cell lines established from pancreatic cancers. NRF2 silencing also decreased the ALDH1A1 and ALDH3A1 expression. Furthermore, this NRF2 depletion enhanced the antiproliferative effects of the chemotherapeutic agent, 5-fluorouracil (5-FU) in pancreatic cancer cells. View Full-Text
Keywords: pancreatic cancer; NRF2; ALDH1A1; ALDH3A1; 5-FU pancreatic cancer; NRF2; ALDH1A1; ALDH3A1; 5-FU

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Duong, H.-Q.; You, K.S.; Oh, S.; Kwak, S.-J.; Seong, Y.-S. Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells. Antioxidants 2017, 6, 52.

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