ArticleOncotarget2016
Gli-1/PI3K/AKT/NF-kB pathway mediates resistance to radiation and is a target for reversion of responses in refractory acute myeloid leukemia cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 72 citations in OpenAlex.
- GANT61 suppresses proliferation and induces apoptosis in ALK-Positive anaplastic large cell lymphoma via modulating the Hh-PIK3IP1-Akt signaling axis.Annals of hematology · 2026Article
- Total Body Irradiation in Haematopoietic Stem Cell Transplantation: A Comprehensive Literature Review and Institutional Experience from the Policlinico of Catania.Medicina (Kaunas, Lithuania) · 2025Review
- Efficacy and Safety of Conditioning Regimen with Chidamide Plus TMI/Cy/Flu Followed by Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk and R/R AML.Stem cell reviews and reports · 2025Article
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Cooperative NF-κB and Notch1 signaling promotes macrophage-mediated MenaINV expression in breast cancer.Breast cancer research : BCR · 2023Article
- Hedgehog signaling and the glioma-associated oncogene in cancer radioresistance.Frontiers in cell and developmental biology · 2023Review
- Canonical Hedgehog Pathway and Noncanonical GLI Transcription Factor Activation in Cancer.Cells · 2022Review
- Characteristics of leukemic stem cells in acute leukemia and potential targeted therapies for their specific eradication.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- The hedgehog pathway in hematopoiesis and hematological malignancy.Frontiers in oncology · 2022Review
- Hedgehog/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside.Frontiers in cell and developmental biology · 2022Review
- Article
- Inhibition of EZH2 by chidamide exerts antileukemia activity and increases chemosensitivity through Smo/Gli-1 pathway in acute myeloid leukemia.Journal of translational medicine · 2021Article
- GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.Cell death & disease · 2021Article
- The roles of NLRP3 inflammasome-mediated signaling pathways in hyperuricemic nephropathy.Molecular and cellular biochemistry · 2021Review
- Tributyrin Plays an Important Role in Regulating the Growth and Health Status of Juvenile Blunt Snout Bream (Frontiers in immunology · 2021Article
- Article
- Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.Signal transduction and targeted therapy · 2020Review
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
- Hedgehog Pathway Inhibitors: A New Therapeutic Class for the Treatment of Acute Myeloid Leukemia.Blood cancer discovery · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Total body irradiation combined with chemotherapy is currently the most effective procedure as a preparative myeloablative regimen. However, resistance to radiotherapy and chemotherapy in refractory acute myeloid leukemia is associated with short-time recurrence after allogeneic hematopoietic stem cell transplantation. To address this issue, we used three cell lines, HL60, HL60/ADR (adriamycin-resistant cells), and HL60/RX (a radiation-resistant cell line established from HL60 cells), as cellular models to investigate the mechanism of the Hedgehog (Hh) signaling pathway resulting in radioresistance, and the efficacy of LDE225 (an inhibitor of the Hh pathway) to enhance radiation sensitivity. Our results indicated that HL60/RX and HL60/ADR cells showed an increased in radioresistance and elevated activity of Hh pathway proteins compared with HL60 cells (P<0.001). In addition, LDE225 significantly reduced clonogenic survival with a sensitivity enhancement ratio (SER) of 1.283 for HL60/ADR and 1.245 for HL60/RX cells. The combination of LDE225 with irradiation significantly increased radiation-induced apoptosis and expression of γ-H2AX and BAK compared with single-treatment groups in both HL60/RX and HL60/ADR cells (P<0.001). In vivo, the combination of LDE225 with irradiation exerted a significant antitumor effect compared with the control and single agents in HL60/RX- and HL60/ADR-xenografted mouse models (P<0.001). Furthermore, our data obtained from western blot and IHC analyses showed that the activation of pAKT and NF-kB was reduced by LDE225 treatment in both HL60/ADR and HL60/RX cells. This demonstrates that the Gli-1/PI3K/AKT/NF-kB pathway plays a key role in resistance to radiation, and that inhibition of the Hh pathway sensitizes cells to radiation by overcoming radioresistance.
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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.