Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression
Autoři:
Pan Zhang aff001; Dan He aff002; Erqun Song aff001; Mingdong Jiang aff003; Yang Song aff001
Působiště autorů:
Key Laboratory of Luminescence and Real-Time Analytical Chemistry, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, P. R. China
aff001; Department of Oncology, Nuclear Industry Hospital, Chengdu, Sichuan, P. R. China
aff002; Department of Radiation Oncology, The Ninth People's Hospital of Chongqing, Chongqing, P. R. China
aff003
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0223760
Souhrn
The current study aimed to identify the radiosensitizing effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in combination with radiotherapy in non-small-cell lung cancer (NSCLC) cells. The combination of celecoxib potentiated radiation-induced apoptosis; however, no changes in cell cycle distribution and number of phosphorylated histone H2AX foci were detected, indicating a DNA damage-independent mechanism. In an in vivo mouse model, the tumor size was significantly decreased in the group combining celecoxib with radiation compared with the radiation only group. Phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), as well as expression of COX-2 were significantly downregulated in cells treated with the combination of celecoxib and radiation compared with the radiation only group. The result indicated that celecoxib exhibits radiosensitizing effects through COX-2 and Akt/mTOR-dependent mechanisms. Induction the Akt/mTOR signaling pathway promotes radioresistance in various cancers, including NSCLC. Therefore, the current study suggested the therapeutic potential of combination therapy of celecoxib and radiation in the prevention of radioresistance.
Klíčová slova:
Cell cycle and cell division – Cancer treatment – Mouse models – Apoptosis – Radiation therapy – Non-small cell lung cancer – NSAIDs – COX-2 inhibitors
Zdroje
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