Knockdown of c‑Myc activates Fas-mediated apoptosis and sensitizes A549 cells to radiation

Zhang,Jing; Zhou,Ling; Nan,Zhaodi; Yuan,Qing; Wen,Jie; Xu,Maolei; Li,Youjie; Li,Baosheng; Wang,Pingyu; Liu,Changmin; Ma,Ying; Chen,Shaoshui; Xie,Shuyang

doi:10.3892/or.2017.5897

Knockdown of c‑Myc activates Fas-mediated apoptosis and sensitizes A549 cells to radiation

Authors:
- Jing Zhang
- Ling Zhou
- Zhaodi Nan
- Qing Yuan
- Jie Wen
- Maolei Xu
- Youjie Li
- Baosheng Li
- Pingyu Wang
- Changmin Liu
- Ying Ma
- Shaoshui Chen
- Shuyang Xie
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Affiliations: Key Laboratory of Tumor Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Oncology, Affiliated Hospital to Binzhou Medical University, Binzhou, Shandong 256603, P.R. China, The Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
Published online on: August 10, 2017 https://doi.org/10.3892/or.2017.5897
Pages: 2471-2479

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Abstract

Several studies have demonstrated that cancer radiosensitivity is associated with the deregulation of c‑Myc, but the relationship between c‑Myc and Fas in radioresistance of lung adenocarcinoma remains unclear. In this study, we established radiation-resistant A549 cell model (A549/R), and investigated the roles of c‑Myc and Fas in radiation-induced cytotoxicity of A549 cells. Apoptosis detection showed that there were fewer apoptotic cells in A549/R cells treated with radiation than in A549 cells. Western blotting results demonstrated the inverse expression pattern of c‑Myc and Fas in A549 and A549/R cells. Suppression of c‑Myc expression by small interfering RNA (siRNA) displayed enhancement of Fas-mediated apoptosis in A549/R cells, accompanying a significant decrease of Bid, Bcl‑2, pro‑caspase‑8, -9 and -3 and increase of Bax. In contrast, Fas-mediated apoptosis was attenuated while Fas expression was suppressed by ectopic expression of c‑Myc in A549 cells. Moreover, decreased cell viability and increased induction of apoptosis were observed in A549/R cells followed by combinational treatment of c‑Myc siRNA and irradiation, whereas, upregulation of c‑Myc reduced the sensitivity of A549 cells to irradiation. These results indicated that c‑Myc and Fas regulated the sensitivity of A549 cells to irradiation by regulating caspase‑8-mediated Bid activation and the subsequent association with the mitochondrial pathway of apoptosis.

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