ArticleBMC cancer2016
Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy.
Article in BMC cancer, 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, 30 citations in OpenAlex.
- Hepatitis B virus hijacks MRE11-RAD50-NBS1 complex to form its minichromosome.PLoS pathogens · 2025Article
- Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer.Materials today. Bio · 2024Article
- Review
- Review
- Impact of DNA damage response defects in cancer cells on response to immunotherapy and radiotherapy.Journal of medical imaging and radiation oncology · 2022Review
- Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.Nature reviews. Clinical oncology · 2022Review
- Intraventricular Meningiomas: Clinical-Pathological and Genetic Features of a Monocentric Series.Current oncology (Toronto, Ont.) · 2022Article
- Rad50 promotes ovarian cancer progression through NF-κB activation.Journal of cellular and molecular medicine · 2021Article
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers.Molecular biomedicine · 2020Article
- Article
- Tetrandrine sensitizes nasopharyngeal carcinoma cells to irradiation by inducing autophagy and inhibiting MEK/ERK pathway.Cancer medicine · 2020Article
- Adjacent mutations in the archaeal Rad50 ABC ATPase D-loop disrupt allosteric regulation of ATP hydrolysis through different mechanisms.Nucleic acids research · 2020Article
- Knockdown of annexin VII enhances nasopharyngeal carcinoma cell radiosensitivity in vivo and in vitro.Cancer biomarkers : section A of Disease markers · 2020Article
- MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment.Molecular cancer · 2019Review
- A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis.American journal of cancer research · 2019Article
- Overexpression of the MRE11-RAD50-NBS1 (MRN) complex in rectal cancer correlates with poor response to neoadjuvant radiotherapy and prognosis.BMC cancer · 2018Article
- Endoplasmic reticulum stress pathway PERK-eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF-κB.Cancer science · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR.
methodsA recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo.
resultsRad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo.
conclusionOur findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption.
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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.