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

• Published in: PloS one 2019-10, Vol.14 (10), p.e0223760-e0223760
• Main Authors: Zhang, Pan, He, Dan, Song, Erqun, Jiang, Mingdong, Song, Yang
• Format: Article
• Language: English
• Subjects: A549 Cells; AKT protein; Analytical chemistry; Angiogenesis; Angiogenesis inhibitors; Animals; Anti-inflammatory agents; Apoptosis; Biology and Life Sciences; Cancer cells; Cancer research; Cancer therapies; Cancer treatment; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - therapy; Celecoxib; Celecoxib - administration & dosage; Celecoxib - pharmacology; Cell cycle; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Cell Survival - drug effects; Cell Survival - radiation effects; Cellular signal transduction; Chemotherapy; COX-2 inhibitors; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Deoxyribonucleic acid; DNA; DNA damage; Drug therapy; EDTA; Education; Endoplasmic reticulum; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Genetic aspects; Histone H2A; Humans; Inflammation; Kinases; Laboratories; Lung cancer; Lung diseases; Lung Neoplasms - metabolism; Lung Neoplasms - therapy; Male; Medicine and Health Sciences; Mice; Non-small cell lung cancer; Non-small cell lung carcinoma; Nonsteroidal anti-inflammatory agents; Nonsteroidal anti-inflammatory drugs; Penicillin; Pharmaceutical sciences; Phosphorylation; Protein kinases; Proto-Oncogene Proteins c-akt - metabolism; Radiation; Radiation (Physics); Radiation effects; Radiation therapy; Radiation-Sensitizing Agents - administration & dosage; Radiation-Sensitizing Agents - pharmacology; Radioresistance; Radiotherapy; Rapamycin; Research and Analysis Methods; Sensitivity enhancement; Signal transduction; Signal Transduction - drug effects; Signal Transduction - radiation effects; Signaling; Small cell lung carcinoma; Studies; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223760

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.