Sirt3 Promoted DNA Damage Repair and Radioresistance Through ATM-Chk2 in Non-small Cell Lung Cancer Cells.
Sirt3 Promoted DNA Damage Repair and Radioresistance Through ATM-Chk2 in Non-small Cell Lung Cancer Cells.
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Sirt3 通过 ATM-Chk2 在非小细胞肺癌细胞中促进 DNA 损伤修复和放射抗性
DOI：
10.7150/jca.53173
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发表时间：
2021
影响因子：
3.9
通讯作者：
Gao F
中科院分区：
文献类型：
--
作者：
Cao K;Chen Y;Zhao S;Huang Y;Liu T;Liu H;Li B;Cui J;Cai J;Bai C;Yang Y;Gao F
目的：放射治疗是肺癌治疗不可缺少的手段，尤其是非小细胞肺癌（NSCLC），发病率和死亡率都很高。然而，细胞对电离辐射的抵抗往往导致治疗失败。本研究旨在探讨Sirt 3在NSCLC放疗中的作用。材料与方法：取80对肺癌组织标本制备组织芯片，免疫组化法检测Sirt 3的表达。采用细胞存活率和凋亡率测定细胞放射敏感性。用γ-H2 AX灶评价DNA损伤。最后，建立了原位肺癌模型，以测试体内放射敏感性。结果：Sirtuin 3（Sirt 3）在非小细胞肺癌细胞系及肺癌组织中表达明显高于正常组织。敲低Sirt 3显著增加辐射诱导的细胞凋亡，并增加细胞存活功效。相反，Sirt 3过表达促进肺癌细胞的放射抗性。Sirt 3基因的敲除也加重了辐射引起的G2/M期细胞阻滞。此外，Sirt 3被发现是关键的ATM-Chk 2途径的激活后照射。最后，我们的体内模型显示，靶向Sirt 3显著地使肺癌对放疗敏感。结论：结论：Sirt 3在NSCLC的放射抵抗中起重要作用，为NSCLC的放射治疗提供了新的靶点和机制。
Objective: Radiotherapy is an indispensable approach for lung cancer, especially for non-small cell lung cancer (NSCLC) with high incidence and mortality. However, cellular resistance to ionizing radiation often results in failure in treatment. In this study, we aimed to investigate the role of Sirt3 in radiotherapy on NSCLC. Materials and Methods: Resected samples from 80 pairs of lung cancer was used to prepare tissue array and Sirt3 was stained with immunochemical method. Cell survival as well as apoptosis assay were used to determine the cellular radiosensitivity. Moreover, DNA damage was evaluated by using γ-H2AX foci. Finally, an in situ lung cancer model to test the radiosensitivity in vivo. Results: Sirtuin 3 (Sirt3) was found upregulated in NSCLC cell lines, as well as lung cancer tissues compared with normal tissues. Knockdown of Sirt3 significantly increased radiation-induced cell apoptosis, and increased cell survival efficacy. In contrast, Sirt3 overexpression promoted radioresistance in lung cancer cells. Sirt3 knockdown also aggravated the G2/M cell cycle arrest caused by irradiation. Furthermore, Sirt3 was found to be critical for the activation of ATM-Chk2 pathway upon irradiation. Finally, our in vivo model showed that targeting Sirt3 significantly sensitized lung cancer to radiotherapy. Conclusion: In conclusion, our findings identified a significant role of Sirt3 in radioresistanct of NSCLC, which provides novel mechanism as well as target for radiotherapy.
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影响因子：
5.2
作者：
Xiong, Yanlu;Wang, Mingxing;Han, Yong
通讯作者：
Han, Yong
DOI：
10.1016/j.bbamcr.2018.09.005
发表时间：
2018-12-01
影响因子：
5.1
作者：
Zhu, Rongying;Yang, Xiaodong;Chen, Yuhchyau
通讯作者：
Chen, Yuhchyau
影响因子：
--
作者：
Yang GC;Fu BC;Zhang DY;Sun L;Chen W;Bai L;Gao T;Lu HG;Wang ZY;Kong QQ;Qiu L;Tian H
通讯作者：
Tian H
影响因子：
--
作者：
Gökyildirim MY;Grandel U;Hattar K;Dahlem G;Schuetz E;Leinberger FH;Eberle F;Sibelius U;Grimminger F;Seeger W;Engenhart-Cabillic R;Dikomey E;Subtil FSB
通讯作者：
Subtil FSB
影响因子：
7.4
作者：
Bhat TA;Kumar S;Chaudhary AK;Yadav N;Chandra D
通讯作者：
Chandra D