Carbon ion triggered immunogenic necroptosis of nasopharyngeal carcinoma cells involving necroptotic inhibitor BCL-x
Autor: | Cihang Bao, Jiade J. Lu, Bilikere S. Dwarakanath, Yun Sun, Chandan Guha, Yuanli Dong, Xiaodong Wu, Lin Kong, Yangle Huang |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cell type Cell cycle checkpoint Necroptosis necroptosis photon-resistant cells 03 medical and health sciences carbon ion irradiation 0302 clinical medicine Immune system Downregulation and upregulation immunogenic cell death medicine mixed lineage kinase domain-like pseudokinase Chemistry nasopharyngeal carcinoma medicine.disease stomatognathic diseases 030104 developmental biology Oncology Nasopharyngeal carcinoma 030220 oncology & carcinogenesis Cancer research Phosphorylation Immunogenic cell death Research Paper |
Zdroj: | Journal of Cancer |
ISSN: | 1837-9664 |
Popis: | To explore the potential and mechanisms of necroptosis, a form of immunogenic cell death, induced by carbon ion as compared to photon beams in established photon resistant- (PR-) and sensitive nasopharyngeal carcinoma (NPC) cells. MLKL is considered a central executor of necroptosis and phosphorylation of MLKL (p-MLKL) was a critical event of necroptosis. The clonogenic survival and DNA microarray demonstrated that after repeated photon irradiation, radiosensitive NPC cells became apoptosis-resistant but could be effectively inhibited by carbon ion irradiation. The relative biologic effectiveness (RBE) at D10 and D37 were 2.15 and 2.78 for PR-NPC cells. Carbon ion induced delayed DNA damage repair, cell cycle arrest, cytogenetic damage, morphological change and cell necrosis, indicating the possibility of necroptosis in both PR- and sensitive NPC cell types. The lower expression of necroptotic inhibitors (caspase-8 and Bcl-x) and higher level of MLKL in PR-NPC cells showed it was relatively more predisposed to necroptosis compared to the sensitive cells. Subsequent experiments demonstrated the significant upregulation of p-MLKL in the PR-NPC cells treated by carbon ion (4 Gy) compared with photon irradiation at both physical (4 Gy) and RBE (10 Gy) doses (P≤0.0001). Moreover, carbon ion induced a robust (up to 28 folds) p-MLKL in the PR-NPC cells as well as sensitive cells (up to 6-fold) coupled with a lower level of BCL-x expression and increased GM-CSF implicated in resculputure of immune system. These results suggested that carbon ion could induce necroptosis of NPC cells, especially in PR-NPC cells, and its mechanisms involve BCL-x. |
Databáze: | OpenAIRE |
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