Celecoxib and Afatinib synergistic enhance radiotherapy sensitivity on human non-small cell lung cancer A549 cells

Abstract

Purpose

Radioresistance is highly correlated with radiotherapy failure in clinical cancer treatment. In the current study, we sought to examine the efficacy of Celecoxib and Afatinib co-treatment as radiosensitizers in the management of non-small cell lung cancer (NSCLC) A549 cells.

Materials and methods

Generally, A549 cells were cultured with the treatment of Celecoxib and/or Afatinib for 24 h. Then, the cells were exposed to irradiation at 2 Gy/min for 1 min. After the end of treatment, cell viability, clonogenic survival, apoptosis and Prostaglandin E2 (PGE2) Elisa assays were performed. Transcriptional levels of Cyclooxygenase-2 (COX-2) affected by Celecoxib and/or Afatinib were measured by RT-qPCR. Posttranscriptional level of epidermal growth factor receptor (EGFR)-related gene was measured by Western blotting analysis.

Results

Here, we, for the first time, reported that the co-treatment of Celecoxib and Afatinib regulates the resistance of NSCLC A549 cells to radiation. The co-treatment of Celecoxib and Afatinib sensitized radiotherapy through the radiation-induced loss of cell viability and colony formation, as well as apoptosis. Mechanistically, Celecoxib and Afatinib-treated cells showed the inhibition of COX-2 and EGFR expression, which may be responsible for the A549 cells’ increased resistance to radiation.

Conclusion

Our results suggested that Celecoxib and Afatinib regulate cell sensitivity to apoptosis, and thus modulate the resistance of NSCLC to radiation.

Keywords:

• Celecoxib
• Afatinib
• radiotherapy
• lung cancer
• radiosensitizer

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Chongqing Health and Family Planning Commission [2017ZDXM030].

Notes on contributors

Pan Zhang

Pan Zhang, PhD, is a postdoctoral researcher with cell biology expertise. Currently working at College of Pharmaceutical Sciences, Southwest University, Chongqing, P. R. China.

Erqun Song

Erqun Song, PhD, Professor, conducts analytical studies for clinical support. Currently working at College of Pharmaceutical Sciences, Southwest University, Chongqing, P. R. China.

Mingdong Jiang

Mingdong Jiang, PhD, Professor, is a clinical radiation oncology doctor. Currently working at Department of Radiation Oncology, The Ninth People’s Hospital of Chongqing, Chongqing, P. R. China

Yang Song

Yang Song, PhD, Professor, is medicinal chemist with experience in development of radiosensitizers. Currently working at College of Pharmaceutical Sciences, Southwest University, Chongqing, P. R. China.