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Enhancement of high-LET radiation-induced apoptosis of lung cancer cells by a synthetic polypeptide derived from a mitochondrial protein SMAC
https://repo.qst.go.jp/records/77551
https://repo.qst.go.jp/records/77551eee2b311-f78f-4544-9cf1-1d3cd5f263e9
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-11-21 | |||||
| タイトル | ||||||
| タイトル | Enhancement of high-LET radiation-induced apoptosis of lung cancer cells by a synthetic polypeptide derived from a mitochondrial protein SMAC | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
勝部, 孝則
× 勝部, 孝則× Xie, Yi× Wang, Bing× Qiang DU, Li× WANG, Yan× XU, Chang× ZHANG, Hong× Katsube, Takanori× Xie, Yi× Wang, Bing |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | X-linked inhibitor of apoptosis protein (XIAP) is frequently upregulated in many malignant cancer cells. Second mitochondrial-derived activator of caspases (SMAC) is a bona fide mitochondrial protein that antagonizes the interaction between XIAP and caspase and promotes apoptosis. The aim of this study is to investigate the radiation-sensitising effect from a mimetic compound of SMAC, ANTP-SmacN7, in lung cancer cells irradiated with high-LET ionizing radiation (IR) from accelerated carbon and iron particles. Two human non-small lung cancer (NSCLC) cell lines with high XIAP expression, A549 and NCI-H460, were irradiated with low-LET X-irradiations or high-LET IR with or without treatment of ANTP-SmacN7. Change of cell survival, induction of apoptosis and cell cycle progression, and alterations in both death and survival signals for apoptosis, were studied by colony formation assay, flowcytometry, and Western blot analysis, respectively. Results showed that high-LET IR was more efficient for clonogenic cell killing and induction of apoptosis than low-LET X-irradiations. In addition, ANTP-SmacN7 markedly promoted apoptosis through inhibition of XIAP and activation of caspase-3 and 9. Furthermore, both antiapoptotic and proapoptotic molecular response was correlated with the apoptotic cell killing and in accordance with the results of clonogenic cell killing. These findings provide useful information to improve high-LET clinical radiotherapy for NSCLC from the point of view of pharmaceutical radio-sensitization. Funding: This work was partially supported by grants from the Key Program of National Natural Science Foundation of China (U1432248); Ministry of science and technology national key R&D project (2016YFC0904600); National Natural Science Foundation of China (11605260, 31670859); CAMS Innovation Fund for Medical Science (2017-I2M-1-016); the Western Talent Program of Chinese Academy of Sciences; Ministry of Education, Culture, Sports, and Science Culture (MEXT) Grant-in-Aid for Scientific Research on Innovative Areas, Grant Number JP15K21745, 15H05944 and 15H05935 “Living in Space”, and Research Project Grant (14J313) with Heavy Ions at NIRS-HIMAC, Japan. Keywords: iron-particle radiation; carbon-particle radiation; non-small lung cancer cells; caspase; radio-sensitizer. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Radiation Research Society Annual Meeting 2019 | |||||
| 発表年月日 | ||||||
| 日付 | 2019-11-03 | |||||
| 日付タイプ | Issued | |||||
