Oridonin Enhances Radiation-Induced Cell Death by Promoting DNA Damage in Non-Small Cell Lung Cancer Cells.
Oridonin Enhances Radiation-Induced Cell Death by Promoting DNA Damage in Non-Small Cell Lung Cancer Cells.
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DOI：
10.3390/ijms19082378
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发表时间：
2018-08-13
影响因子：
5.6
通讯作者：
Lee HJ
中科院分区：
文献类型：
--
作者：
Park H;Jeong YJ;Han NK;Kim JS;Lee HJ
尽管已经进行了许多尝试来提高放射治疗癌症的疗效，但放射抵抗仍然是肺癌治疗的障碍。冬凌草甲素是一种天然化合物，具有很好的抗肿瘤功效，可引发癌细胞死亡;然而，其直接的细胞靶点、作为放射增敏剂的功效和潜在的活性机制仍不清楚。本文报道了冬凌草甲素对H460非小细胞肺癌细胞株的细胞毒活性和抗肿瘤活性。我们通过增殖、克隆形成、活性氧（ROS）产生、DNA损伤和凋亡测定评估了冬凌草甲素的作用。在体外，冬凌草甲素增强辐射诱导的细胞生长抑制和克隆存活。冬凌草甲素还促进辐射诱导的ROS产生和DNA损伤，并增强细胞凋亡。在体内，冬凌草甲素和辐射的组合有效地抑制H460异种移植肿瘤的生长，与单独辐射相比，具有更高的caspase-3活化和H2 A组蛋白家族成员X（H2 AX）磷酸化。我们的研究结果表明，冬凌草甲素具有一种新的机制，通过增加DNA损伤和细胞凋亡，以提高放射治疗反应。结论：冬凌草甲素可能是一种新的小分子药物，可改善非小细胞肺癌的放射治疗效果。
Although many attempts have been made to improve the efficacy of radiotherapy to treat cancer, radiation resistance is still an obstacle in lung cancer treatment. Oridonin is a natural compound with promising antitumor efficacy that can trigger cancer cell death; however, its direct cellular targets, efficacy as a radiosensitizer, and underlying mechanisms of activity remain unclear. Herein, we report that oridonin exhibits additive cytotoxic and antitumor activity with radiation using the H460 non-small cell lung cancer cell lines. We assessed the effect of oridonin by proliferation, clonogenic, reactive oxygen species (ROS) production, DNA damage, and apoptosis assays. In vitro, oridonin enhanced the radiation-induced inhibition of cell growth and clonogenic survival. Oridonin also facilitated radiation-induced ROS production and DNA damage and enhanced apoptotic cell death. In vivo, the combination of oridonin and radiation effectively inhibited H460 xenograft tumor growth, with higher caspase-3 activation and H2A histone family member X (H2AX) phosphorylation compared with that of radiation alone. Our findings suggest that oridonin possesses a novel mechanism to enhance radiation therapeutic responses by increasing DNA damage and apoptosis. In conclusion, oridonin may be a novel small molecule to improve radiotherapy in non-small cell lung cancer.
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冬凌草甲素通过 ROS 激活的 NF-κB 信号稳定视黄酸受体 α
影响因子：
3.8
作者：
Cao Y;Wei W;Zhang N;Yu Q;Xu WB;Yu WJ;Chen GQ;Wu YL;Yan H
通讯作者：
Yan H
DOI：
10.1155/2016/6146595
发表时间：
2016
期刊：
Analytical cellular pathology (Amsterdam)
影响因子：
--
作者：
Malik A;Sultana M;Qazi A;Qazi MH;Parveen G;Waquar S;Ashraf AB;Rasool M
通讯作者：
Rasool M
影响因子：
3.5
作者：
Chang, Joe Y.;Cox, James D.
通讯作者：
Cox, James D.
影响因子：
5.7
作者：
Ikezoe, T;Yang, Y;Taguchi, H
通讯作者：
Taguchi, H
DNA 损伤、死亡受体激活和活性氧是紫外线辐射诱导细胞凋亡的基本和独立方式
影响因子：
8
作者：
Kulms, D;Zeise, E;Schwarz, T
通讯作者：
Schwarz, T