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Updated: Jan 5, 2026
Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Inhibition of Aurora A enhances radiosensitivity in selected lung cancer cell lines
Ningbo Liu1, Yong Antican Wang2,3, Yunguang Sun3,4
1Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Oncology Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin, 300060, China. liuningbo@tjmuch.com.
Background:
In 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).
Methods:
Here, 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.
Results:
We 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.
Conclusions:
Taken 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.
Insights
Increased Aurora kinase A (AURKA) expression correlates with poorer survival in non-small cell lung cancer (NSCLC). AURKA inhibition combined with radiotherapy shows promise, particularly in P53-competent NSCLC, warranting further investigation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Aurora serine/threonine kinases regulate mitosis and chromosomal stability.
- Aurora kinase A (AURKA) is an oncogene implicated in various cancers.
- The prognostic value of AURKA and its role in NSCLC radiotherapy remain unclear.
Purpose of the Study:
- To investigate the correlation between AURKA expression and patient survival in NSCLC.
- To evaluate the efficacy of AURKA inhibition combined with radiotherapy in NSCLC models.
- To explore the role of P53 in mediating sensitivity to AURKA inhibition and radiotherapy.
Main Methods:
- Immunohistochemistry (IHC) to assess AURKA expression in 63 NSCLC samples.
- MTS and clonogenic assays to evaluate cell survival and radiosensitivity upon AURKA inhibition with MLN8237.
- In vivo xenograft models to assess the combined effect of MLN8237 and radiation.
Main Results:
- Increased AURKA expression correlated with decreased time to progression and overall survival in NSCLC patients.
- MLN8237 inhibited cell growth in a partially P53-dependent manner.
- Combining MLN8237 with radiotherapy demonstrated enhanced tumor growth delay in vivo, with efficacy influenced by P53 status.
Conclusions:
- AURKA expression is a negative prognostic marker in NSCLC.
- Targeting AURKA with MLN8237 in combination with radiotherapy is a potential therapeutic strategy for NSCLC.
- P53 status influences response to AURKA inhibition and radiotherapy, suggesting potential for P53 modulation to overcome resistance.
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