ArticleInternational journal of molecular medicine2019
Downregulation of Keap1 contributes to poor prognosis and Axitinib resistance of renal cell carcinoma via upregulation of Nrf2 expression.
Article in International journal of molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- TSC22D4 drives clear cell renal cell carcinoma progression and therapy resistance by stabilizing NRF2 through KEAP1 disruption.Cell death & disease · 2026Article
- Nrf2 Signaling in Renal Cell Carcinoma: A Potential Candidate for the Development of Novel Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Metabolic Rate and Oxidative Stress as a Risk Factors in the Development of Colorectal Cancer.International journal of molecular sciences · 2024Article
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Frontier knowledge and future directions of programmed cell death in clear cell renal cell carcinoma.Cell death discovery · 2024Review
- Exploring the multifaceted antitumor activity of axitinib in lung carcinoids.Frontiers in endocrinology · 2024Article
- Targeting ferroptosis: a new therapeutic opportunity for kidney diseases.Frontiers in immunology · 2024Review
- Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy.Frontiers in pharmacology · 2024Article
- High Expression of NRF2 and Low Expression of KEAP1 Predict Worse Survival in Patients With Operable Triple-Negative Breast Cancer.Journal of breast cancer · 2023Article
- NRF2: KEAPing Tumors Protected.Cancer discovery · 2022Article
- Integrative clinical and molecular characterization of translocation renal cell carcinoma.Cell reports · 2022Article
- Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Keap1-Nrf2 Pathway Regulates ALDH and Contributes to Radioresistance in Breast Cancer Stem Cells.Cells · 2021Article
- Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma.Cancers · 2020Review
- MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells.Cell death & disease · 2020Article
- Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Long Non-Coding RNA PVT1 Regulates the Resistance of the Breast Cancer Cell Line MDA-MB-231 to Doxorubicin via Nrf2.Technology in cancer research & treatmentArticle
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kelch‑like ECH‑associated protein 1 (Keap1)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling has a protective effect on normal cells. A number of previous studies demonstrated that Keap1/Nrf2 signaling is associated with drug resistance in numerous tumors. The aim of the present study was to investigate the roles of Keap1 in renal cell carcinoma (RCC) and its effect on sensitivity to chemotherapy. Reverse transcription‑quantitative polymerase chain reaction was used to detect the mRNA expression of Keap1 in 45 cases of RCC tumors and adjacent normal tissues. A total of five randomly selected patients with RCC, five RCC cell lines and normal renal tubular cells were examined to detect the protein and mRNA expressions of Keap1. The 5‑year survival rate was analyzed by Kaplan‑Meier analysis. The cell viability was assessed by a Cell Counting kit‑8 assay. The cell apoptosis and reactive oxygen species (ROS) were determined by flow cytometry. The expressions of associated proteins were determined by western blot analysis. It was identified that in RCC tissues and RCC cell lines, the expression of Keap1 was downregulated, which was considered to be associated with poor prognosis. In total, 1 µM Axitinib significantly decreased cell viability, promoted ROS release and induced cell apoptosis in ACHN cells. Silencing Keap1 was able to reverse the inhibitory effect of Axitinib and enhance the protein expressions of Nrf2, NAD(P)H dehydrogenase [quinone] 1 and heme oxygenase 1. However, silencing Nrf2 increased the cell sensitivity to Axitinib. Under Axitinib condition, overexpressing Nrf2 was able to increase cell viability; however, overexpressing Keap1 resulted in an opposite effect. Keap1 serves as a tumor suppressor; its low expression was associated with poor prognosis and a decreased sensitivity of RCC cells to Axitinib. A possible mechanism underlying Axitinib resistance may involve Nrf2 overexpression.
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