ArticleRadiation research2014
Ionizing radiation sensitizes breast cancer cells to Bcl-2 inhibitor, ABT-737, through regulating Mcl-1.
Article in Radiation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer.Radiation oncology (London, England) · 2015Trial
- Overcoming ABT-737 resistance in triple-negative breast cancer: C-phycocyanin-mediated myeloid cell leukemia-1 downregulation enhances apoptotic sensitivity.Molecular biology reports · 2026Article
- Advanced drug delivery platforms targeting cellular senescence: A promising strategy for cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- BH3 mimetic and dual PI3K/mTOR inhibitor attenuates gemcitabine resistance in triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2025Article
- Molecular Mechanisms of Radiation Resistance in Breast Cancer: A Systematic Review of Radiosensitization Strategies.Current issues in molecular biology · 2025Review
- Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.Expert reviews in molecular medicine · 2024Review
- PANoptosis: a potential new target for programmed cell death in breast cancer treatment and prognosis.Apoptosis : an international journal on programmed cell death · 2024Review
- Article
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- Senescence and the tumor-immune landscape: Implications for cancer immunotherapy.Seminars in cancer biology · 2022Review
- Bcl-xL inhibition radiosensitizesCancer research communications · 2022Article
- Exploiting senescence for the treatment of cancer.Nature reviews. Cancer · 2022Review
- Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs.International journal of molecular sciences · 2022Review
- ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model.Yonsei medical journal · 2022Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Bcl-2/Bcl-xL inhibitor ABT-263 overcomes hypoxia-driven radioresistence and improves radiotherapy.Cell death & disease · 2021Article
- 225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models.Cancer medicine · 2021Article
- Chemical, Physical and Biological Triggers of Evolutionary Conserved Bcl-xL-Mediated Apoptosis.Cancers · 2020Article
- Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma.Biological research · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Breast-conserving surgery followed by radiation therapy has become the standard of care for early stage breast cancer. However, there are some patients that develop a local failure. We have previously shown that Bcl-2 overexpression was associated with an increased risk of local recurrence in patients with early stage breast cancer. The purpose of this study was to explore an approach to overcome radiation resistance by targeting pro-survival Bcl-2 family proteins in breast cancer cells. The breast cancer cell lines MCF-7, ZR-75-1 and MDA-MB231 were used in this study. siRNAs were employed to silence myeloid cell leukemia 1 (Mcl-1). A small molecule inhibitor of Bcl-2, ABT-737, was used to target anti-apoptotic Bcl-2 family proteins. Apoptosis was identified by FITC Annexin V, PI staining and Western blot analysis. The sensitivity to ionizing radiation and ABT-737 were measured by clonogenic assays. The effect of radiation and ABT-737 was also tested in a MCF-7 xenograft mouse model. Our data demonstrate that the combination of ABT-737 and radiation-induced apoptosis had an inhibitory effect on breast cancer cell proliferation. However, treatment with ABT-737 resulted in elevated Mcl-1 in breast cancer cell lines. Targeting Mcl-1 by siRNA sensitized MCF-7 cells to ABT-737. We revealed that radiation blunted Mcl-1 elevation induced by ABT-737, and that radiation downregulated Mcl-1 by promoting its degradation. Our results indicate that radiation and ABT-737 exert a synergistic effect on breast cancer cell lines through downregulating Mcl-1 and activating the bak-apoptotic pathway. These results support the combination of radiation and pro-survival Bcl-2 family inhibitor as a potential novel therapeutic strategy in the local-regional management of breast cancer.
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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.