ArticleMedical oncology (Northwood, London, England)2010
Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway.
Article in Medical oncology (Northwood, London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- A randomized phase II trial of nab-paclitaxel and gemcitabine with tarextumab or placebo in patients with untreated metastatic pancreatic cancer.Cancer medicine · 2019Trial
- Notch 3 regulates ferroptosis of lens epithelial cells in age-related cataract by PI3K/AKT pathway.Indian journal of ophthalmology · 2026Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.Cancer science · 2024Article
- Glycogen synthase kinase 3β: the nexus of chemoresistance, invasive capacity, and cancer stemness in pancreatic cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- NOTCH3 missense mutations as predictor of long-term response to gemcitabine in a patient with epithelioid hemangioendothelioma.Journal of cancer research and clinical oncology · 2023Review
- Krüppel-like factor 10 modulates stem cell phenotypes of pancreatic adenocarcinoma by transcriptionally regulating notch receptors.Journal of biomedical science · 2023Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.Cancer chemotherapy and pharmacology · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Elevated expression of nuclear receptor-binding SET domain 3 promotes pancreatic cancer cell growth.Cell death & disease · 2021Article
- Article
- The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies.Frontiers in molecular biosciences · 2021Review
- The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.Frontiers in cell and developmental biology · 2021Review
- Review
- Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients.Cancer management and research · 2019Article
- The Role ofThe oncologist · 2018Review
- Specific inhibitor of Notch‑3 enhances the sensitivity of NSCLC cells to gemcitabine.Oncology reports · 2018Article
- Identification of genes and pathways associated with MDR in MCF-7/MDR breast cancer cells by RNA-seq analysis.Molecular medicine reports · 2018Article
- A phase I trial of the γ-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma.British journal of cancer · 2018Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch3 is one of the four Notch receptors identified in mammal, but its role in human pancreatic cancer remains poorly characterized. In this study, we sought to determine the effect of suppressing Notch3 expression on the chemosensitivity to gemcitabine in human pancreatic cancer cell lines BxPC-3 and PANC-1. RNA interference was used to suppress Notch3 expression. Gemcitabine-induced cytotoxicity was determined by MTT. Cell apoptosis was measured by flow cytometry. Caspase 3 activity was assayed using a Caspase Fluorescent Assay Kit. The effect of Notch3-specific siRNA on PI3K/Akt activity was also quantified. Notch3-specific siRNA suppressed Notch3 expression, and furthermore increased gemcitabine-induced, caspase-mediated apoptosis. The suppression of Notch3 expression decreased the average IC(50) in BxPC-3 and PANC-1 cells treated with gemcitabine. PI3K/Akt activity was decreased by the suppression of Notch3 expression. Taken together, these data demonstrated that Notch3 is a potential therapeutic target for pancreatic cancer, and PI3K/Akt is a key signaling component by which activation of the Notch3 signal transduction pathway protects pancreatic cancer cells from chemotherapy-induced cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.