ArticleBritish journal of cancer2013
Autophagy inhibition induces enhanced proapoptotic effects of ZD6474 in glioblastoma.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- Review
- Low-frequency magnetic field therapy for glioblastoma: Current advances, mechanisms, challenges and future perspectives.Journal of advanced research · 2025Review
- DDX3X dynamics, glioblastoma's genetic landscape, therapeutic advances, and autophagic interplay.Medical oncology (Northwood, London, England) · 2024Review
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Sensitivity of osteosarcoma cell lines to autophagy inhibition as determined by pharmacologic and genetic manipulation.Veterinary and comparative oncology · 2023Article
- Review
- Autophagy Inhibition Enhances Anti-Glioblastoma Effects of Pyrazolo[3,4-Life (Basel, Switzerland) · 2022Article
- A Review of Neuroprotective Effects and Mechanisms of Ginsenosides From Panax Ginseng in Treating Ischemic Stroke.Frontiers in pharmacology · 2022Review
- Autophagy induced by Vip3Aa has a pro-survival role inVirulence · 2021Article
- Review
- Deciphering the Role of Autophagy in Treatment of Resistance Mechanisms in Glioblastoma.International journal of molecular sciences · 2021Review
- New Insights into Therapy-Induced Progression of Cancer.International journal of molecular sciences · 2020Review
- The impact of autophagy during the development and survival of glioblastoma.Open biology · 2020Review
- Manipulation of Mitophagy by "All-in-One" nanosensitizer augments sonodynamic glioma therapy.Autophagy · 2020Article
- ANXA6 Contributes to Radioresistance by Promoting Autophagy via Inhibiting the PI3K/AKT/mTOR Signaling Pathway in Nasopharyngeal Carcinoma.Frontiers in cell and developmental biology · 2020Article
- The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance.Frontiers in pharmacology · 2020Review
- Modulating autophagy as a therapeutic strategy for the treatment of paediatric high-grade glioma.Brain pathology (Zurich, Switzerland) · 2019Review
- Review
- Gefitinib-mediated apoptosis is enhanced via inhibition of autophagy by chloroquine diphosphate in cutaneous squamous cell carcinoma cells.Oncology letters · 2019Article
- Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation.Cell death & disease · 2019Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutophagy is a lysosomal degradation pathway that can provide energy through its recycling mechanism to act as a cytoprotective adaptive response mediating treatment resistance in cancer cells. We investigated the autophagy-inducing effects of ZD6474, a small-molecule inhibitor that blocks activities of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET tyrosine kinases.
methodsWe investigated the effects of ZD6474 on autophagy in glioblastomas cells. The ZD6474 mechanism of action was determined by western blot. We then examined the impacts of the inhibition of autophagy in combination with ZD6474 on cell apoptosis in vitro. Furthermore, we evaluated the synergistic anticancer activity of combination treatment with an autophagy inhibitor (chloroquine) and ZD6474 in U251 glioblastoma cells xenograft model.
resultsZD6474-induced autophagy was dependent on signalling through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. ZD6474-induced autophagy was inhibited by both knockdown of the ATG7 and Beclin 1 gene, essential autophagy genes, and pharmacologic agents (chloroquine and 3-methyalanine) treatment. Both treatments also dramatically sensitised glioblastoma cells to ZD6474-induced apoptosis, decreasing cell viability in vitro. Furthermore, in a xenograft mouse model, combined treatment with ZD6474 and chloroquine significantly inhibited U251 tumour growth, and increased the numbers of apoptotic cells compared with treatment with either agent alone.
conclusionAutophagy protects glioblastoma cells from the proapoptotic effects of ZD6474, which might contribute to tumour resistance against ZD6474 treatment.
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