ArticleAutophagy2008
Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer.
Article in Autophagy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 167 citations in OpenAlex.
- mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review).International journal of oncology · 2026Review
- Caspase-independent cell death in lung cancer: from mechanisms to clinical applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Anti-Cancer Strategy Based on Changes in the Role of Autophagy Depending on the Survival Environment and Tumorigenesis Stages.Molecules (Basel, Switzerland) · 2024Review
- Crosstalk between metabolism and cell death in tumorigenesis.Molecular cancer · 2024Review
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
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- Sphingosine 1-phosphate lyase facilitates cancer progression through converting sphingolipids to glycerophospholipids.Clinical and translational medicine · 2022Article
- Article
- Autophagy Agents in Clinical Trials for Cancer Therapy: A Brief Review.Current oncology (Toronto, Ont.) · 2022Review
- The functional mechanism of bone marrow-derived mesenchymal stem cells in the treatment of animal models with Alzheimer's disease: crosstalk between autophagy and apoptosis.Stem cell research & therapy · 2022Review
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
- Role of autophagy in tumor response to radiation: Implications for improving radiotherapy.Frontiers in oncology · 2022Review
- The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.Molecular biology reports · 2021Review
- Article
- The function of LncRNAs and their role in the prediction, diagnosis, and prognosis of lung cancer.Clinical and translational medicine · 2021Review
- Therapy-Induced Tumor Cell Death: Friend or Foe of Immunotherapy?Frontiers in oncology · 2021Review
- Pink1/PARK2/mROS-Dependent Mitophagy Initiates the Sensitization of Cancer Cells to Radiation.Oxidative medicine and cellular longevity · 2021Article
- The Role of Mitochondria in Vascular Calcification.Journal of translational internal medicine · 2020Review
- Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Autophagy has been reported to be increased in irradiated cancer cells resistant to various apoptotic stimuli. We therefore hypothesized that induction of autophagy via mTOR inhibition could enhance radiosensitization in apoptosis-inhibited H460 lung cancer cells in vitro and in a lung cancer xenograft model. To test this hypothesis, combinations of Z-DEVD (caspase-3 inhibitor), RAD001 (mTOR inhibitor) and irradiation were tested in cell and mouse models. The combination of Z-DEVD and RAD001 more potently radiosensitized H460 cells than individual treatment alone. The enhancement in radiation response was not only evident in clonogenic survival assays, but also was demonstrated through markedly reduced tumor growth, cellular proliferation (Ki67 staining), apoptosis (TUNEL staining) and angiogenesis (vWF staining) in vivo. Additionally, upregulation of autophagy as measured by increased GFP-LC3-tagged autophagosome formation accompanied the noted radiosensitization in vitro and in vivo. The greatest induction of autophagy and associated radiation toxicity was exhibited in the tri-modality treatment group. Autophagy marker, LC-3-II, was reduced by 3-methyladenine (3-MA), a known inhibitor of autophagy, but further increased by the addition of lysosomal protease inhibitors (pepstatin A and E64d), demonstrating that there is autophagic induction through type III PI3 kinase during the combined therapy. Knocking down of ATG5 and beclin-1, two essential autophagic molecules, resulted in radiation resistance of lung cancer cells. Our report suggests that combined inhibition of apoptosis and mTOR during radiotherapy is a potential therapeutic strategy to enhance radiation therapy in patients with non-small cell lung cancer.
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What OpenQuestion holds
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.