ArticleCancer cell international2020
Inhibition of Delta-like Ligand 4 enhances the radiosensitivity and inhibits migration in cervical cancer via the reversion of epithelial-mesenchymal transition.
Article in Cancer cell international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 14 citations in OpenAlex.
- Emerging landscape of oncogenic signaling pathways in cervical cancer.Discover oncology · 2026Review
- Csep1P protein from Campylobacter concisus induces a chemokine-dominant inflammatory state in macrophages and enhances proinflammatory response to gut bacteria.PLoS pathogens · 2026Article
- Elevated POSTN expression predicts poor prognosis and is associated with radioresistance in cervical cancer patients treated with radical radiotherapy.Scientific reports · 2025Article
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- 2Molecular imaging and biology · 2024Article
- Identification of key genes to predict response to chemoradiotherapy and prognosis in esophageal squamous cell carcinoma.Frontiers in molecular biosciences · 2024Article
- Bufalin inhibits epithelial-mesenchymal transition and increases radiosensitivity of non-small cell lung cancer via inhibition of the Src signaling.Journal of thoracic disease · 2023Article
- Notch Signaling in Vascular Endothelial and Mural Cell Communications.Cold Spring Harbor perspectives in medicine · 2022Article
- Radiotherapy resistance: identifying universal biomarkers for various human cancers.Journal of cancer research and clinical oncology · 2022Review
- A 25 Immune-Related Gene Pair Signature Predicts Overall Survival in Cervical Cancer.Cancer informatics · 2022Article
- Article
- Notch signaling in female cancers: a multifaceted node to overcome drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma.Frontiers in pharmacology · 2021Article
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7 authors at 1 institution in 1 country.
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Abstract
backgroundConcurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells.
methodsThe expression of DLL4 and epithelial-mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity was evaluated using the CCK8 assay, flow cytometry, Transwell assays for cell invasion and migration, and Immunofluorescence staining in vitro.
resultsThe expression of DLL4 in radiotherapy-resistant SiHa cells was significantly higher than that in radiotherapy-sensitive Me-180 cells. Furthermore, downregulation of DLL4 enhanced the radiosensitivity of SiHa and Caski cells via the inhibition of cell proliferation, promotion of radiation-induced apoptosis, and inhibition of the DNA damage repair. Moreover, downregulation of DLL4 inhibited the EMT and reduced the proliferation, invasion, and migration ability in SiHa and Caski cells. Consistent with the DLL4 expression in the cell lines, the expression of DLL4 in the tissues of the radioresistant group was also higher than that of the radiosensitive group.
conclusionsDownregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).
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