ArticleRespiratory research2019
Inhibition of Aurora A enhances radiosensitivity in selected lung cancer cell lines.
Article in Respiratory research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- A 13-gene prognostic model developed using machine learning to predict the response to neoadjuvant chemoradiotherapy in rectal carcinoma.Cancer cell international · 2026Article
- Enhanced Delivery of Aurora Kinase A Inhibitor Alisertib via Tumor-Targeting Immunoliposome Nanocomplex for Improved Treatment of Cancers Including Atypical Teratoid/Rhabdoid Tumor.International journal of nanomedicine · 2026Article
- Telaglenastat as an alternative to cisplatin as a radiosensitizer in the treatment of head and neck squamous cell carcinoma.Cancer letters · 2024Article
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- Article
- Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review.Translational lung cancer research · 2024Review
- A genomic score to predict local control among patients with brain metastases managed with radiation.Neuro-oncology · 2023Article
- Article
- Systematic analysis of transcriptome signature for improving outcomes in lung adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- Emerging roles of Aurora-A kinase in cancer therapy resistance.Acta pharmaceutica Sinica. B · 2023Review
- Aurora B Inhibitors as Cancer Therapeutics.Molecules (Basel, Switzerland) · 2023Review
- A Review of Radiation-Induced Alterations of Multi-Omic Profiles, Radiation Injury Biomarkers, and Countermeasures.Radiation research · 2023Review
- RBL2/DREAM-mediated repression of the Aurora kinase A/B pathway determines therapy responsiveness and outcome in p53 WT NSCLC.Scientific reports · 2022Article
- Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer.Frontiers in oncology · 2022Review
- Network Pharmacology and Comparative Transcriptome Reveals Biotargets and Mechanisms of Curcumol Treating Lung Adenocarcinoma Patients With COVID-19.Frontiers in nutrition · 2022Article
- The role of radiotherapy-related autophagy genes in the prognosis and immune infiltration in lung adenocarcinoma.Frontiers in immunology · 2022Article
- Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing.American journal of cancer research · 2021Article
- Comprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma.Journal of cell communication and signaling · 2020Article
- Review
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7 authors.
Funding
Abstract
backgroundIn mammalian cells, Aurora serine/threonine kinases (Aurora A, B, and C) are expressed in a cell cycle-dependent fashion as key mitotic regulators required for the maintenance of chromosomal stability. Aurora-A (AURKA) has been proven to be an oncogene in a variety of cancers; however, whether its expression relates to patient survival and the association with radiotherapy remains unclear in non-small cell lung cancer (NSCLC).
methodsHere, we first analyzed AURKA expression in 63 NSCLC tumor samples by immunohistochemistry (IHC) and used an MTS assay to compare cell survival by targeting AURKA with MLN8237 (Alisertib) in H460 and HCC2429 (P53-competent), and H1299 (P53-deficient) cell lines. The radiosensitivity of MLN8237 was further evaluated by clonogenic assay. Finally, we examined the effect of combining radiation and AURKA inhibition in vivo with a xenograft model and explored the potential mechanism.
resultsWe found that increased AURKA expression correlated with decreased time to progression and overall survival (p = 0.0447 and 0.0096, respectively). AURKA inhibition using 100 nM MLN8237 for 48 h decreases cell growth in a partially P53-dependent manner, and the survival rates of H460, HCC2429, and H1299 cells were 56, 50, and 77%, respectively. In addition, the survival of H1299 cells decreased 27% after ectopic restoration of P53 expression, and the radiotherapy enhancement was also influenced by P53 expression (DER H460 = 1.33; HCC2429 = 1.35; H1299 = 1.02). Furthermore, tumor growth of H460 was delayed significantly in a subcutaneous mouse model exposed to both MLN8237 and radiation.
conclusionsTaken together, our results confirmed that the expression of AURKA correlated with decreased NSCLC patient survival, and it might be a promising inhibition target when combined with radiotherapy, especially for P53-competent lung cancer cells. Modulation of P53 function could provide a new option for reversing cell resistance to the AURKA inhibitor MLN8237, which deserves further investigation.
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