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cIAP1/2 are involved in the radiosensitizing effect of birinapant on NSCLC cell line in vitro |
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| Authors: | Hao Sun Yanan Du Ming Yao Qin Wang Kaihua Ji Liqing Du Chang Xu Ningning He Jinhan Wang Manman Zhang Yang Liu Yan Wang Kaixue Wen Qiang Liu |
| Institution: | 1. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China;2. Tianjin Center for Disease Control and Prevention, Tianjin, China
Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (lead), Methodology (lead), Software (equal), Validation (lead), Visualization (equal), Writing - original draft (lead);3. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Methodology (equal), Validation (equal);4. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Methodology (supporting);5. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Funding acquisition (supporting), Methodology (supporting);6. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Methodology (supporting), Visualization (supporting);7. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Formal analysis (supporting), Funding acquisition (supporting);8. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Funding acquisition (supporting), Methodology (supporting), Software (supporting);9. Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China Contribution: Formal analysis (supporting), Methodology (supporting);10. Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Shanxi, China |
| Abstract: | Tumour radioresistance is a major problem for cancer radiation therapy. To identify the underlying mechanisms of this resistance, we used human non-small cell lung cancer (NSCLC) cell lines and focused on the Inhibitor of Apoptosis Protein (IAP) family, which contributes to tumourigenesis and chemoresistance. We investigated the possible correlation between radioresistance in six NSCLC cell lines and IAP protein levels and tested the radiosensitizing effect of birinapant in vitro, a molecule that mimics the second mitochondria-derived activator of caspase. We found that birinapant-induced apoptosis and inhibited the proliferation of NSCLC cells after exposure to radiation. These effects were induced by birinapant downregulation of cIAP protein levels and changes of cIAP gene expression. Overall, birinapant can inhibit tumour growth of NSCLC cell lines to ironizing radiation and act as a promising strategy to overcome radioresistance in NSCLC. |
| Keywords: | apoptosis birinapant IAP family NSCLC radiosensitive |