ArticleCell death & disease2017
NDRG1 inhibition sensitizes osteosarcoma cells to combretastatin A-4 through targeting autophagy.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The prognostic value of decreased NDRG1 expression in patients with digestive system cancers: A meta-analysis.Medicine · 2018Pooled it
- Bibliometric analysis of autophagy in the diagnosis and treatment of osteosarcoma: a bibliometric analysis (2007-2023).Cancer biology & therapy · 2025Article
- The Interplay Between Autophagy and Apoptosis in the Mechanisms of Action of Stilbenes in Cancer Cells.Antioxidants (Basel, Switzerland) · 2025Review
- Expression Profile of miR-199a and Its Role in the Regulation of Intestinal Inflammation.Animals : an open access journal from MDPI · 2023Article
- NDRG1 in Cancer: A Suppressor, Promoter, or Both?Cancers · 2022Review
- The Ni(II)-Binding Activity of the Intrinsically Disordered Region of Human NDRG1, a Protein Involved in Cancer Development.Biomolecules · 2022Article
- Review
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- Role of Plant-Derived Active Constituents in Cancer Treatment and Their Mechanisms of Action.Cells · 2022Review
- Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.International journal of molecular sciences · 2021Review
- CXCR4 blockade sensitizes osteosarcoma to doxorubicin by inducing autophagic cell death via PI3K‑Akt‑mTOR pathway inhibition.International journal of oncology · 2021Article
- NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation.Journal of orthopaedic surgery and research · 2021Article
- NDRG1 facilitates lytic replication of Kaposi's sarcoma-associated herpesvirus by maintaining the stability of the KSHV helicase.PLoS pathogens · 2021Article
- Markers of acute toxicity of DDT exposure in pancreatic beta-cells determined by a proteomic approach.PloS one · 2020Article
- Targeting autophagy is a promising therapeutic strategy to overcome chemoresistance and reduce metastasis in osteosarcoma.International journal of oncology · 2019Review
- Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A.International journal of biological sciences · 2019Article
- Insight Into the Role of Autophagy in Osteosarcoma and Its Therapeutic Implication.Frontiers in oncology · 2019Review
- MicroRNA-136 functions as a tumor suppressor in osteosarcoma via regulating metadherin.Cancer biomarkers : section A of Disease markers · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combretastatin A-4 (CA-4), a tubulin-depolymerizing agent, shows promising antitumor efficacy and has been under several clinical trials in solid tumors for 10 years. Autophagy has an important pro-survival role in cancer therapy, thus targeting autophagy may improve the efficacy of antitumor agents. N-myc downstream-regulated gene 1 (NDRG1) is a significant stress regulatory gene, which mediates cell survival and chemoresistance. Here we reported that CA-4 could induce cell-protective autophagy, and combination treatment of CA-4 and autophagy inhibitor chloroquine (CQ) exerted synergistic cytotoxic effect on human osteosarcoma (OS) cells. Meanwhile, CA-4 or CQ could increase the expression of NDRG1 independently. We further performed mechanistic study to explore how CA-4 and CQ regulate the expression of NDRG1. Using luciferase reporter assay, we found that CA-4 transcriptionally upregulated NDRG1 expression, whereas CQ triggered colocalization of NDRG1 and lysosome, which subsequently prevented lysosome-dependent degradation of NDRG1. Further, we showed that knockdown of NDRG1 caused the defect of lysosomal function, which accumulated LC3-positive autophagosomes by decreasing their fusion with lysosomes. Moreover, NDRG1 inhibition increased apoptosis in response to combination treatment with CA-4 and CQ. Taken together, our study revealed abrogation of NDRG1 expression sensitizes OS cells to CA-4 by suppression of autophagosome-lysosome fusion. These results provide clues for developing more effective cancer therapeutic strategies by the concomitant treatment with CA-4 and clinical available autophagy inhibitors.
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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.