ArticleDigestive diseases and sciences2013
The noncytotoxic dose of sorafenib sensitizes Bel-7402/5-FU cells to 5-FU by down-regulating 5-FU-induced Nrf2 expression.
Article in Digestive diseases and sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
- Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Konjac glucomannan enhances 5-FU-induced cytotoxicity of hepatocellular carcinoma cells via TLR4/PERK/CHOP signaling to induce endoplasmic reticulum stress.Oncology research · 2022Article
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- Article
- Nrf2 Is a Potential Modulator for Orchestrating Iron Homeostasis and Redox Balance in Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases.Cancers · 2020Review
- Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib.Medicina (Kaunas, Lithuania) · 2019Review
- LncRNA FOXD2-AS1 as a competitive endogenous RNA against miR-150-5p reverses resistance to sorafenib in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2019Article
- Potential Applications of NRF2 Inhibitors in Cancer Therapy.Oxidative medicine and cellular longevity · 2019Review
- Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance.Cancers · 2018Review
- Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma.Cancer medicine · 2018Article
- miR-144 reverses chemoresistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway.American journal of translational research · 2016Article
- CpG oligodeoxynucleotides enhance chemosensitivity of 5-fluorouracil in HepG2 human hepatoma cells via downregulation of the antiapoptotic factors survivin and livin.Cancer cell international · 2013Article
Corrections and comments
- Retraction · 2023-08-04Concerns/Issues about Image · Duplication of/in Image · Manipulation of Images · Original Data and/or Images not Provided and/or not Available · Unreliable Data ·
- Retracted
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcquired resistance to 5-fluorouracil (5-FU) is a serious therapeutic obstacle in advanced hepatocellular carcinoma (HCC) patients.
aimTo investigate whether nuclear factor erythroid 2-related factor 2 (Nrf2) was associated with drug resistance in 5-FU resistant Bel-7402 (Bel-7402/5-FU) cells, and if sorafenib, an oral multikinase inhibitor targeting the tumor and vasculature, could reverse drug resistance in Bel-7402/5-FU cells at the noncytotoxic dosage.
methodsWe used MTT to detect the resistance reversal activity of sorafenib, compared Nrf2 expression in various conditions by western blot and qRT-PCR, and analyzed subcellular localization of Nrf2 by immunofluorescence.
resultsThe endogenous expression of Nrf2 in Bel-7402/5-FU cells was similar to that observed in Bel-7402 cells. However, Nrf2 expression levels were increased by 5-FU treatment in Bel-7402/5-FU cells higher than that in Bel-7402 cells, which is to highlight the Nrf2 contribution to the enhanced resistance of Bel-7402/5-FU cells to 5-FU. Moreover, intracellular Nrf2 protein level was significantly down-regulated by Nrf2-shRNA in Bel-7402/5-FU cells, resulting in partial reversal of 5-FU resistance. Sorafenib down-regulated the increased expression of Nrf2 induced by 5-FU treatment and partly reversed 5-FU resistance in Bel-7402/5-FU cells.
conclusionsThese results suggested that more sensitive cell defense mediated by Nrf2 was associated with drug resistance of Bel-7402/5-FU cells. Sorafenib reversed drug resistance, and its reversal mechanism might be due to the suppression of Nrf2 expression induced by 5-FU, indicating the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs in HCC patients.
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