ArticleCellular signalling2015
HSP90 inhibitor NVP-AUY922 enhances TRAIL-induced apoptosis by suppressing the JAK2-STAT3-Mcl-1 signal transduction pathway in colorectal cancer cells.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- A Phase II Study of Ganetespib as Second-line or Third-line Therapy for Metastatic Pancreatic Cancer.American journal of clinical oncology · 2018Trial
- NPLOC4 Constructs Tumor Immunosuppressive Microenvironment in Pan-cancer and Hepatocellular Carcinoma.Current medicinal chemistry · 2026Article
- Exploring WNT pathway dysregulation in serrated colorectal cancer for improved diagnostic and therapeutic strategies.Frontiers in genetics · 2025Article
- Luteolin inhibits diffuse large B-cell lymphoma cell growth through the JAK2/STAT3 signaling pathway.Frontiers in pharmacology · 2025Article
- AutoEdge-CCP: A novel approach for predicting cancer-associated circRNAs and drugs based on automated edge embedding.PLoS computational biology · 2024Article
- Ailanthone suppresses the activity of human colorectal cancer cells through the STAT3 signaling pathway.International journal of molecular medicine · 2022Article
- IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma.Frontiers in immunology · 2022Article
- The heat shock response and small molecule regulators.European journal of medicinal chemistry · 2021Review
- AUY922 induces retinal toxicity through attenuating TRPM1.Journal of biomedical science · 2021Article
- Elucidation of the Molecular Pathways Involved in the Protective Effects of AUY-922 in LPS-Induced Inflammation in Mouse Lungs.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Traditional Chinese medicines and their active ingredients sensitize cancer cells to TRAIL-induced apoptosis.Journal of Zhejiang University. Science. B · 2021Review
- Analysis of Genome-Wide Alternative Splicing Profiling and Development of Potential Drugs in Lung Adenocarcinoma.Frontiers in genetics · 2021Article
- STAT3 and p53: Dual Target for Cancer Therapy.Biomedicines · 2020Review
- Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells.Journal of Cancer · 2020Article
- MLAA-34 knockdown shows enhanced antitumor activity via JAK2/STAT3 signaling pathway in acute monocytic leukemia.Journal of Cancer · 2020Article
- Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer.OncoTargets and therapy · 2020Review
- Hsp90 inhibitors enhance the antitumoral effect of osimertinib in parental and osimertinib-resistant non-small cell lung cancer cell lines.Translational lung cancer research · 2019Article
- Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways.BMC cell biology · 2018Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer.Oncotarget · 2018Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
TRAIL has been shown to induce apoptosis in cancer cells, but in some cases, certain cancer cells are resistant to this ligand. In this study, we explored the ability of representative HSP90 (heat shock protein 90) inhibitor NVP-AUY922 to overcome TRAIL resistance by increasing apoptosis in colorectal cancer (CRC) cells. The combination of TRAIL and NVP-AUY922 induced synergistic cytotoxicity and apoptosis, which was mediated through an increase in caspase activation. The treatment of NVP-AUY922 dephosphorylated JAK2 and STAT3 and decreased Mcl-1, which resulted in facilitating cytochrome c release. NVP-AUY922-mediated inhibition of JAK2/STAT3 signaling and down-regulation of their target gene, Mcl-1, occurred in a dose and time-dependent manner. Knock down of Mcl-1, STAT3 inhibitor or JAK2 inhibitor synergistically enhanced TRAIL-induced apoptosis. Taken together, our results suggest the involvement of the JAK2-STAT3-Mcl-1 signal transduction pathway in response to NVP-AUY922 treatment, which may play a key role in NVP-AUY922-mediated sensitization to TRAIL. By contrast, the effect of the combination treatments in non-transformed colon cells was minimal. We provide a clinical rationale that combining HSP90 inhibitor with TRAIL enhances therapeutic efficacy without increasing normal tissue toxicity in CRC patients.
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