Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells.
Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells.
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DOI：
10.18632/oncotarget.3535
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Ding WQ
中科院分区：
文献类型：
--
作者：
Gu Q;He Y;Ji J;Yao Y;Shen W;Luo J;Zhu W;Cao H;Geng Y;Xu J;Zhang S;Cao J;Ding WQ
放射治疗是治疗不能手术的非小细胞肺癌（NSCLC）的重要手段。然而，最近的证据表明，辐射可以促进几种类型的癌症的侵袭和转移，其潜在机制尚未完全了解。本研究旨在探讨放射增强NSCLC细胞侵袭力的分子机制。我们发现，照射后，缺氧诱导因子1α（HIF-1α）增加并移位到细胞核中，在那里它与CXCR 4启动子中的缺氧反应元件（HRE）结合，促进CXCR 4的转录。此外，活性氧（ROS）也在辐射诱导的CXCR 4表达中发挥作用。结果显示，2戈伊X射线照射可促进H1299、A549和H460细胞的转移和侵袭能力，SDF-1α处理后可显著增强上述作用。阻断SDF-1α/CXCR 4的相互作用可抑制NSCLC细胞的辐射侵袭能力。PI 3 K/pAkt和MAPK/pERK 1/2通路参与了辐射诱导的基质金属蛋白酶（MMP）表达。在体内，辐射促进了H1299细胞在肝脏和肺中的定植，这是由CXCR 4介导的。总之，我们的研究结果阐明了辐射增强NSCLC细胞侵袭力的潜在机制。
Radiotherapy is an important procedure for the treatment of inoperable non-small cell lung cancer (NSCLC). However, recent evidence has shown that irradiation can promote the invasion and metastasis of several types of cancer, and the underlying mechanisms are not fully understood. This study aimed to investigate the molecular mechanism by which radiation enhances the invasiveness of NSCLC cells. We found that after irradiation, hypoxia-inducible factor 1α (HIF-1α) was increased and translocated into the nucleus, where it bound to the hypoxia response element (HRE) in the CXCR4 promoter and promoted the transcription of CXCR4. Furthermore, reactive oxygen species (ROS) also plays a role in the radiation-induced expression of CXCR4. Our results revealed that 2 Gy X-ray irradiation promoted the metastasis and invasiveness of H1299, A549 and H460 cells, which were significantly enhanced by SDF-1α treatment. Blocking the SDF-1α/CXCR4 interaction could suppress the radiation-induced invasiveness of NSCLC cells. The PI3K/pAkt and MAPK/pERK1/2 pathways were found to be involved in radiation-induced matrix metalloproteinase (MMP) expression. In vivo, irradiation promoted the colonization of H1299 cells in the liver and lung, which was mediated by CXCR4. Altogether, our findings have elucidated the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells.
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影响因子：
2.3
作者：
Antonelli, Manila;Massimino, Maura;Giangaspero, Felice
通讯作者：
Giangaspero, Felice
通过缺氧对趋化因子受体CXCR4的调节。
DOI：
10.1084/jem.20030267
发表时间：
2003-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
HIV-TAT 介导的铜/锌超氧化物歧化酶-1 (SOD1) 蛋白转导可保护皮肤细胞免受电离辐射。
DOI：
10.1186/1748-717x-8-253
发表时间：
2013-10-31
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Gu Q;Feng T;Cao H;Tang Y;Ge X;Luo J;Xue J;Wu J;Yang H;Zhang S;Cao J
通讯作者：
Cao J
影响因子：
82.9
作者：
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分子对肿瘤细胞缺氧的反应。
影响因子：
37.3
作者：
Kunz, Manfred;Ibrahim, Saleh M
通讯作者：
Ibrahim, Saleh M