ArticlePloS one2016
AZD2014 Radiosensitizes Oral Squamous Cell Carcinoma by Inhibiting AKT/mTOR Axis and Inducing G1/G2/M Cell Cycle Arrest.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Identification of Cuproptosis-Related Patterns Predict Prognosis and Immunotherapy Response in Hepatocellular Carcinoma.Journal of cellular and molecular medicine · 2024Article
- Diterpenoid fromInternational journal of molecular sciences · 2024Article
- A zebrafish xenotransplant model of anaplastic thyroid cancer to study tumor microenvironment and innate immune cell interactions in vivo.Endocrine-related cancer · 2024Article
- PAK4-relevant proliferation reduced by cell autophagy via p53/mTOR/p-AKT signaling.Translational cancer research · 2023Article
- Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas.International journal of molecular sciences · 2022Review
- Inhibition of the Translation Initiation Factor eIF4A Enhances Tumor Cell Radiosensitivity.Molecular cancer therapeutics · 2022Article
- Chrysophanol Suppresses Cell Growth via mTOR/PPAR-α Regulation and ROS Accumulation in Cultured Human Tongue Squamous Carcinoma SAS Cells.Current issues in molecular biology · 2022Article
- Translation Initiation Machinery as a Tumor Selective Target for Radiosensitization.International journal of molecular sciences · 2021Review
- [Antitumor effects of AZD2014, a dual mTORC1/2 inhibitor, against human hepatocellular carcinoma xenograft in nude mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Article
- PI3k inhibitors (BKM120 and BYL719) as radiosensitizers for head and neck squamous cell carcinoma during radiotherapy.PloS one · 2021Article
- Targeting AKT/mTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials.International journal of molecular sciences · 2020Review
- Triptolide induces protective autophagy and apoptosis in human cervical cancer cells by downregulating Akt/mTOR activation.Oncology letters · 2018Article
- Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.Cellular and molecular life sciences : CMLS · 2018Review
- Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells.Histochemistry and cell biology · 2017Article
- Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinomaOncotarget · 2017Article
- Oleic acid induces apoptosis and autophagy in the treatment of Tongue Squamous cell carcinomas.Scientific reports · 2017Article
- Transcriptomic characterization of differential gene expression in oral squamous cell carcinoma: a meta-analysis of publicly available microarray data sets.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models.
methodsWe isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression.
resultsCombination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells.
conclusionsThese findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma.
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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.